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1
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Cardinali CEF, Fabiano de Freitas C, Sonchini Gonçalves R, Amanda Pedroso de Morais F, Nunes de Lima Martins J, Martins YA, Fernando Comar J, de Souza Bonfim-Mendonça P, Tessaro AL, Kimura E, Caetano W, Hioka N, Brunaldi K, Ravanelli MI. "Effects of Redox Status on Immediate Hypericin-Mediated Photodynamic Therapy in Human Glioblastoma T98G Cell Line". ACS OMEGA 2025; 10:1100-1109. [PMID: 39829538 PMCID: PMC11740150 DOI: 10.1021/acsomega.4c08553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/13/2024] [Accepted: 12/19/2024] [Indexed: 01/22/2025]
Abstract
Glioblastoma Multiforme (GBM) is one of the most aggressive types of brain tumor. GBM can modulate glutathione (GSH) levels and regulate cellular redox state, which can explain its high resistance to chemotherapeutic agents. Photodynamic therapy (PDT) is a selective, nontoxic, and minimally invasive treatment approved for many types of cancer. PDT leads to cell death mainly by promoting the generation of reactive oxygen species (ROS). Thus, in the current study, PDT with the photosensitizer hypericin (Hyp), formulated in mixed 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/biotinylated-pluronic F127 (F127-B) liposomes, in combination with the GSH synthesis inhibitor buthionine sulfoximine (BSO) were tested against T98G cell line of human glioblastoma. The mixed liposome was effective in delivering Hyp to the cells, leading to a dose relationship between Hyp and ROS levels. BSO potentiated Hyp cell uptake, decreased GSH levels regardless of Hyp concentration, and intensified ROS generation for 1.00 and 5.00 μmol L-1 Hyp. Nonetheless, cell death was more pronounced in the groups not treated with BSO, indicating that reduced GSH levels are not a decisive factor in achieving the PDT effects of Hyp. In conclusion, the mixed DPPC/F127-B liposomes were effective as a delivery system for Hyp. However, the combination of BSO and Hyp was not capable of optimizing PDT against T98G cells.
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Affiliation(s)
| | - Camila Fabiano de Freitas
- Department
of Chemistry, Federal University of Santa
Catarina (UFSC), Florianópolis, Santa Catarina 88040-380, Brazil
| | | | | | | | - Yandara Akamine Martins
- Departament
of Physiological Sciences, State University
of Maringa, Maringa, Parana 87020-900, Brazil
| | | | | | - André Luiz Tessaro
- Chemistry
Graduation (COLIQ), Federal Technological
University of Parana, Apucarana, Parana 86800-000, Brazil
| | - Elza Kimura
- Department
of Pharmacy and Pharmacology, State University
of Maringa, Maringa, Parana 87020-900, Brazil
| | - Wilker Caetano
- Departament
of Chemistry, State University of Maringa, Maringa, Parana 87020-900, Brazil
| | - Noboru Hioka
- Departament
of Chemistry, State University of Maringa, Maringa, Parana 87020-900, Brazil
| | - Kellen Brunaldi
- Departament
of Physiological Sciences, State University
of Maringa, Maringa, Parana 87020-900, Brazil
| | - Maria Ida Ravanelli
- Departament
of Physiological Sciences, State University
of Maringa, Maringa, Parana 87020-900, Brazil
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2
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Aebisher D, Woźnicki P, Czarnecka-Czapczyńska M, Dynarowicz K, Szliszka E, Kawczyk-Krupka A, Bartusik-Aebisher D. Molecular Determinants for Photodynamic Therapy Resistance and Improved Photosensitizer Delivery in Glioma. Int J Mol Sci 2024; 25:8708. [PMID: 39201395 PMCID: PMC11354549 DOI: 10.3390/ijms25168708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 08/02/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Gliomas account for 24% of all the primary brain and Central Nervous System (CNS) tumors. These tumors are diverse in cellular origin, genetic profile, and morphology but collectively have one of the most dismal prognoses of all cancers. Work is constantly underway to discover a new effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound-a photosensitizer (PS)-which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating the activation processes leading to the formation of reactive oxygen species and the selective destruction of inappropriate cells. Research focusing on the effective use of PDT in glioma therapy is already underway with promising results. In our work, we provide detailed insights into the molecular changes in glioma after photodynamic therapy. We describe a number of molecules that may contribute to the resistance of glioma cells to PDT, such as the adenosine triphosphate (ATP)-binding cassette efflux transporter G2, glutathione, ferrochelatase, heme oxygenase, and hypoxia-inducible factor 1. We identify molecular targets that can be used to improve the photosensitizer delivery to glioma cells, such as the epithelial growth factor receptor, neuropilin-1, low-density lipoprotein receptor, and neuropeptide Y receptors. We note that PDT can increase the expression of some molecules that reduce the effectiveness of therapy, such as Vascular endothelial growth factor (VEGF), glutamate, and nitric oxide. However, the scientific literature lacks clear data on the effects of PDT on many of the molecules described, and the available reports are often contradictory. In our work, we highlight the gaps in this knowledge and point to directions for further research that may enhance the efficacy of PDT in the treatment of glioma.
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Affiliation(s)
- David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of The Rzeszów University, 35-310 Rzeszów, Poland
| | - Paweł Woźnicki
- English Division Science Club, Medical College of The Rzeszów University, 35-310 Rzeszów, Poland;
| | - Magdalena Czarnecka-Czapczyńska
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15 Street, 41-902 Bytom, Poland;
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of The University of Rzeszów, 35-310 Rzeszów, Poland;
| | - Ewelina Szliszka
- Department of Microbiology and Immunology, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15 Street, 41-902 Bytom, Poland;
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of The Rzeszów University, 35-310 Rzeszów, Poland;
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3
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Ma J, Yuan H, Zhang J, Sun X, Yi L, Li W, Li Z, Fu C, Zheng L, Xu X, Wang X, Wang F, Yin D, Yuan J, Xu C, Li Z, Peng X, Wang J. An ultrasound-activated nanoplatform remodels tumor microenvironment through diverse cell death induction for improved immunotherapy. J Control Release 2024; 370:501-515. [PMID: 38703950 DOI: 10.1016/j.jconrel.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 04/30/2024] [Accepted: 05/01/2024] [Indexed: 05/06/2024]
Abstract
Although nanomaterial-based nanomedicine provides many powerful tools to treat cancer, most focus on the "immunosilent" apoptosis process. In contrast, ferroptosis and immunogenic cell death, two non-apoptotic forms of programmed cell death (PCD), have been shown to enhance or alter the activity of the immune system. Therefore, there is a need to design and develop nanoplatforms that can induce multiple modes of cell death other than apoptosis to stimulate antitumor immunity and remodel the immunosuppressive tumor microenvironment for cancer therapy. In this study, a new type of multifunctional nanocomposite mainly consisting of HMME, Fe3+ and Tannic acid, denoted HFT NPs, was designed and synthesized to induce multiple modes of cell death and prime the tumor microenvironment (TME). The HFT NPs consolidate two functions into one nano-system: HMME as a sonosensitizer for the generation of reactive oxygen species (ROS) 1O2 upon ultrasound irradiation, and Fe3+ as a GSH scavenger for the induction of ferroptosis and the production of ROS ·OH through inorganic catalytic reactions. The administration of HFT NPs and subsequent ultrasound treatment caused cell death through the consumption of GSH, the generation of ROS, ultimately inducing apoptosis, ferroptosis, and immunogenic cell death (ICD). More importantly, the combination of HFT NPs and ultrasound irradiation could reshape the TME and recruit more T cell infiltration, and its combination with immune checkpoint blockade anti-PD-1 antibody could eradicate tumors with low immunogenicity and a cold TME. This new nano-system integrates sonodynamic and chemodynamic properties to achieve outstanding therapeutic outcomes when combined with immunotherapy. Collectively, this study demonstrates that it is possible to potentiate cancer immunotherapy through the rational and innovative design of relatively simple materials.
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Affiliation(s)
- Jingbo Ma
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Haitao Yuan
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Jingjing Zhang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Xin Sun
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Letai Yi
- Inner Mongolia Medical University, Hohhot, PR China
| | - Weihua Li
- Medical Imaging Department, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518035, PR China
| | - Zhifen Li
- School of Chemistry and Chemical Engineering, Shanxi Datong University, Datong, Shanxi Province 037009, PR China
| | - Chunjin Fu
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Liuhai Zheng
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Xiaolong Xu
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Xiaoxian Wang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Fujing Wang
- Department of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, PR China
| | - Da Yin
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China
| | - Jimin Yuan
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China.
| | - Chengchao Xu
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; College of Integrative Medicine, Laboratory of Pathophysiology, Key Laboratory of Integrative Medicine on Chronic Diseases, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
| | - Zhijie Li
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China.
| | - Xin Peng
- Ningbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China.
| | - Jigang Wang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, PR China; Department of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, PR China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
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4
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Mazepa E, Furlanetto ALDDM, Brum H, Nakao LS, Martinez PA, Cadena SMSC, Rocha MEM, Cunha ES, Martinez GR. Effects of redox modulation on quiescin/sulfhydryl oxidase activity of melanoma cells. Mol Cell Biochem 2024; 479:511-524. [PMID: 37103678 DOI: 10.1007/s11010-023-04745-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 04/14/2023] [Indexed: 04/28/2023]
Abstract
Secreted quiescin/sulfhydryl oxidase (QSOX) is overexpressed in many tumor cell lines, including melanoma, and is usually associated with a pro-invasive phenotype. Our previous work described that B16-F10 cells enter in a quiescent state as a protective mechanism against damage generated by reactive oxygen species (ROS) during melanogenesis stimulation. Our present results show that QSOX activity was two-fold higher in cells with stimulated melanogenesis when compared to control cells. Considering that glutathione (GSH) is one of the main factor responsible for controlling redox homeostasis in cells, this work also aimed to investigate the relationship between QSOX activity, GSH levels and melanogenesis stimulation in B16-F10 murine melanoma cell line. The redox homeostasis was impaired by treating cells with GSH in excess or depleting its intracellular levels through BSO treatment. Interestingly, GSH-depleted cells without stimulation of melanogenesis kept high levels of viability, suggesting a possible adaptive mechanism of survival even under low GSH levels. They also showed lower extracellular activity of QSOX, and higher QSOX intracellular immunostaining, suggesting that this enzyme was less excreted from cells and corroborating with a diminished extracellular QSOX activity. On the other hand, cells under melanogenesis stimulation showed a lower GSH/GSSG ratio (8:1) in comparison with control (non-stimulated) cells (20:1), indicating a pro-oxidative state after stimulation. This was accompanied by decreased cell viability after GSH-depletion, no alterations in QSOX extracellular activity, but higher QSOX nucleic immunostaining. We suggest that melanogenesis stimulation and redox impairment caused by GSH-depletion enhanced the oxidative stress in these cells, contributing to additional alterations of its metabolic adaptive response.
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Affiliation(s)
- Ester Mazepa
- Postgraduate Program in Sciences (Biochemistry), Department of Biochemistry and Molecular Biology, UFPR, Curitiba, PR, Brazil
| | | | - Hulyana Brum
- Postgraduate Program in Sciences (Biochemistry), Department of Biochemistry and Molecular Biology, UFPR, Curitiba, PR, Brazil
| | | | | | | | - Maria Eliane Merlin Rocha
- Postgraduate Program in Sciences (Biochemistry), Department of Biochemistry and Molecular Biology, UFPR, Curitiba, PR, Brazil
| | - Elizabeth Sousa Cunha
- Postgraduate Program in Sciences (Biochemistry), Department of Biochemistry and Molecular Biology, UFPR, Curitiba, PR, Brazil
| | - Glaucia Regina Martinez
- Postgraduate Program in Sciences (Biochemistry), Department of Biochemistry and Molecular Biology, UFPR, Curitiba, PR, Brazil.
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5
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Aebisher D, Przygórzewska A, Myśliwiec A, Dynarowicz K, Krupka-Olek M, Bożek A, Kawczyk-Krupka A, Bartusik-Aebisher D. Current Photodynamic Therapy for Glioma Treatment: An Update. Biomedicines 2024; 12:375. [PMID: 38397977 PMCID: PMC10886821 DOI: 10.3390/biomedicines12020375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 02/02/2024] [Accepted: 02/03/2024] [Indexed: 02/25/2024] Open
Abstract
Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease.
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Affiliation(s)
- David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of the Rzeszów University, 35-959 Rzeszów, Poland
| | - Agnieszka Przygórzewska
- English Division Science Club, Medical College of the Rzeszów University, 35-025 Rzeszów, Poland;
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the Rzeszów University, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the Rzeszów University, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Magdalena Krupka-Olek
- Clinical Department of Internal Medicine, Dermatology and Allergology, Medical University of Silesia in Katowice, M. Sklodowskiej-Curie 10, 41-800 Zabrze, Poland; (M.K.-O.); (A.B.)
| | - Andrzej Bożek
- Clinical Department of Internal Medicine, Dermatology and Allergology, Medical University of Silesia in Katowice, M. Sklodowskiej-Curie 10, 41-800 Zabrze, Poland; (M.K.-O.); (A.B.)
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of the Rzeszów University, 35-025 Rzeszów, Poland;
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6
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Yu X, Wang X, Yamazaki A. Mn-Si-based nanoparticles-enhanced inhibitory effect on tumor growth and metastasis in photo-immunotherapy. Colloids Surf B Biointerfaces 2023; 226:113314. [PMID: 37060652 DOI: 10.1016/j.colsurfb.2023.113314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/07/2023] [Accepted: 04/11/2023] [Indexed: 04/17/2023]
Abstract
The anticancer effect of phototherapy has been limited by some factors, including the easy degradation of photo agents, the complex tumor microenvironment, and the limited immune activation capacity, which impedes its efficiency in inhibiting tumor growth and tumor metastasis. Herein, Mn-doped mesoporous silica nanoparticles were synthesized to load the photo agent of IR 780, which were further coated with Mn (IMM). Notably, the combination of IMM and an 808 nm laser irradiation simultaneously inhibited the growth of primary tumors and distant untreated tumors in a bilateral animal model, which could be attributed to the protection of IMM to IR 780, the regulation functions to the tumor microenvironment, as well as the enhanced immune activation capacity. This work highlighted an alternative strategy for enhancing the inhibitory effect on both tumor growth and tumor metastasis in the combinational anticancer therapy of phototherapy and immunotherapy (photo-immunotherapy).
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Affiliation(s)
- Xueping Yu
- Graduate School of Creative Science and Engineering, Waseda University, 3-4-1 Shin-Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
| | - Xiupeng Wang
- Health and Medical Research Institute, Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
| | - Atsushi Yamazaki
- Graduate School of Creative Science and Engineering, Waseda University, 3-4-1 Shin-Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
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7
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Peng J, Du K, Sun J, Yang X, Wang X, Zhang X, Song G, Feng F. Photocatalytic Generation of Hydrogen Radical (H⋅) with GSH for Photodynamic Therapy. Angew Chem Int Ed Engl 2023; 62:e202214991. [PMID: 36537886 DOI: 10.1002/anie.202214991] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/16/2022] [Accepted: 12/20/2022] [Indexed: 01/26/2023]
Abstract
As a reactive hydrogen species, the hydrogen radical (H⋅) scarcely sees applications in tumor biological therapy due to the very limited bio-friendly sources of H⋅. In this work, we report that TAF can act as an organic photosensitizer as well as an efficient photocatalytic H⋅ generator with reduced glutathione (GSH) as a fuel. The photoactivation of TAF leads to cell death in two ways including triple amplification of oxidative stress via ferroptosis-apoptosis under normoxia and apoptosis through biological reductions under hypoxia. TAF presents excellent biosafety with ultrahigh photocytotoxicity index at an order of magnitude of 102 -103 on both normoxic and hypoxic cells. The in vitro data suggest that H⋅ therapy is promising to overcome the challenge of tumor hypoxia at low doses of both photocatalyst and light. In addition, the capability of near-infrared two-photon excitation would benefit broad biological applications.
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Affiliation(s)
- Jinlei Peng
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China
| | - Ke Du
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China
| | - Jian Sun
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China.,Current address: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China
| | - Xianli Yang
- State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China
| | - Xia Wang
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China
| | - Xiaoran Zhang
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China
| | - Gang Song
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China.,Current address: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China
| | - Fude Feng
- MOE Key Laboratory of High Performance Polymer Materials and Technology, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, Nanjing, 210023, P. R. China
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8
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Kolarikova M, Hosikova B, Dilenko H, Barton-Tomankova K, Valkova L, Bajgar R, Malina L, Kolarova H. Photodynamic therapy: Innovative approaches for antibacterial and anticancer treatments. Med Res Rev 2023. [PMID: 36757198 DOI: 10.1002/med.21935] [Citation(s) in RCA: 84] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 12/07/2022] [Accepted: 01/03/2023] [Indexed: 02/10/2023]
Abstract
Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.
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Affiliation(s)
- Marketa Kolarikova
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Barbora Hosikova
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Hanna Dilenko
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Katerina Barton-Tomankova
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Lucie Valkova
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Robert Bajgar
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Lukas Malina
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Hana Kolarova
- Department of Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
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9
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Peng J, Du K, Sun J, Yang X, Wang X, Zhang X, Song G, Feng F. Photocatalytic Generation of Hydrogen Radical (H⋅) with GSH for Photodynamic Therapy. Angew Chem Int Ed Engl 2023. [DOI: 10.1002/ange.202214991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Jinlei Peng
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
| | - Ke Du
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
| | - Jian Sun
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
- Current address: Beijing National Laboratory for Molecular Sciences Key Laboratory of Organic Solids Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China
| | - Xianli Yang
- State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
| | - Xia Wang
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
| | - Xiaoran Zhang
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
| | - Gang Song
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
- Current address: Beijing National Laboratory for Molecular Sciences Key Laboratory of Organic Solids Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China
| | - Fude Feng
- MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science and Engineering School of Chemistry and Chemical Engineering Nanjing University Jiangsu Nanjing 210023 P. R. China
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10
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Khorsandi K, Hosseinzadeh R, Esfahani H, Zandsalimi K, Shahidi FK, Abrahamse H. Accelerating skin regeneration and wound healing by controlled ROS from photodynamic treatment. Inflamm Regen 2022; 42:40. [PMID: 36192814 PMCID: PMC9529607 DOI: 10.1186/s41232-022-00226-6] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 08/16/2022] [Indexed: 11/24/2022] Open
Abstract
Cellular metabolisms produce reactive oxygen species (ROS) which are essential for cellular signaling pathways and physiological functions. Nevertheless, ROS act as “double-edged swords” that have an unstable redox balance between ROS production and removal. A little raise of ROS results in cell proliferation enhancement, survival, and soft immune responses, while a high level of ROS could lead to cellular damage consequently protein, nucleic acid, and lipid damages and finally cell death. ROS play an important role in various pathological circumstances. On the contrary, ROS can show selective toxicity which is used against cancer cells and pathogens. Photodynamic therapy (PDT) is based on three important components including a photosensitizer (PS), oxygen, and light. Upon excitation of the PS at a specific wavelength, the PDT process begins which leads to ROS generation. ROS produced during PDT could induce two different pathways. If PDT produces control and low ROS, it can lead to cell proliferation and differentiation. However, excess production of ROS by PDT causes cellular photo damage which is the main mechanism used in cancer treatment. This review summarizes the functions of ROS in living systems and describes role of PDT in production of controllable ROS and finally a special focus on current ROS-generating therapeutic protocols for regeneration and wound healing.
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Affiliation(s)
- Khatereh Khorsandi
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran. .,Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20037, USA.
| | - Reza Hosseinzadeh
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran.,Academic center for education, culture and research, Urmia, Iran
| | - HomaSadat Esfahani
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
| | - Kavosh Zandsalimi
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
| | - Fedora Khatibi Shahidi
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa
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11
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Savyuk MO, Turubanova VD, Mishchenko TA, Lermontova SA, Klapshina LG, Krysko DV, Vedunova MV. Unraveling of Functional Activity of Primary Hippocampal Neuron-Glial Networks in Photodynamic Therapy Based on Tetracyanotetra(aryl)porphyrazines. Cells 2022; 11:cells11071212. [PMID: 35406776 PMCID: PMC8997601 DOI: 10.3390/cells11071212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 03/29/2022] [Accepted: 04/01/2022] [Indexed: 02/04/2023] Open
Abstract
The current efforts in photodynamic therapy (PDT) of brain cancer are focused on the development of novel photosensitizers with improved photodynamic properties, targeted specific localization, and sensitivity to the irradiation dose, ensuring the effectiveness of PDT with fewer side effects for normal nerve tissue. Here, we characterize the effects of four photosensitizers of the tetracyanotetra(aryl)porphyrazine group (pz I–IV) on the functional activity of neuron-glial networks in primary hippocampal cultures in their application in normal conditions and under PDT. The data revealed that the application of pz I–IV leads to a significant decrease in the main parameters of the functional calcium activity of neuron-glial networks and pronounced changes in the network characteristics. The observed negative effects of pz I–IV were aggravated under PDT. Considering the significant restructuring of the functional architectonics of neuron-glial networks that can lead to severe impairments in synaptic transmission and loss of brain functions, and the feasibility of direct application of PDT based on pz I–IV in the therapy of brain tumors is highly controversial. Nevertheless, the unique properties of pz I–IV retain a great prospect of their use in the therapy of tumors of another origin and cellular metabolism.
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Affiliation(s)
- Maria O. Savyuk
- Department of Basic and Medical Genetics, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia; (M.O.S.); (V.D.T.); (T.A.M.); (D.V.K.)
| | - Victoria D. Turubanova
- Department of Basic and Medical Genetics, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia; (M.O.S.); (V.D.T.); (T.A.M.); (D.V.K.)
- Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia
| | - Tatiana A. Mishchenko
- Department of Basic and Medical Genetics, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia; (M.O.S.); (V.D.T.); (T.A.M.); (D.V.K.)
- Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia
| | - Svetlana A. Lermontova
- Sector of Chromophors for Medicine, G.A. Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences, 49 Tropinin st., 603137 Nizhny Novgorod, Russia; (S.A.L.); (L.G.K.)
| | - Larisa G. Klapshina
- Sector of Chromophors for Medicine, G.A. Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences, 49 Tropinin st., 603137 Nizhny Novgorod, Russia; (S.A.L.); (L.G.K.)
| | - Dmitri V. Krysko
- Department of Basic and Medical Genetics, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia; (M.O.S.); (V.D.T.); (T.A.M.); (D.V.K.)
- Cell Death Investigation and Therapy Laboratory (CDIT), Department of Human Structure and Repair, Ghent University, C. Heymanslaan 10, Building B3, 4th Floor, 9000 Ghent, Belgium
- Cancer Research Institute Ghent, 9000 Ghent, Belgium
| | - Maria V. Vedunova
- Department of Basic and Medical Genetics, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia; (M.O.S.); (V.D.T.); (T.A.M.); (D.V.K.)
- Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., 603022 Nizhny Novgorod, Russia
- Correspondence: ; Tel.: +7-915-937-55-55
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12
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Lu J, Jiang Z, Ren J, Zhang W, Li P, Chen Z, Zhang W, Wang H, Tang B. One‐Pot Synthesis of Multifunctional Carbon‐Based Nanoparticle‐Supported Dispersed Cu
2+
Disrupts Redox Homeostasis to Enhance CDT. Angew Chem Int Ed Engl 2022. [DOI: 10.1002/ange.202114373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Jun Lu
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Zhongyao Jiang
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Jie Ren
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Wei Zhang
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Ping Li
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Zhenzhen Chen
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Wen Zhang
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Hui Wang
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan 250014 P. R. China
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13
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In vitro assessment of synergistic effects in combinations of a temoporfin-based photodynamic therapy with glutathione peroxidase 1 inhibitors. Photodiagnosis Photodyn Ther 2021; 36:102478. [PMID: 34375776 DOI: 10.1016/j.pdpdt.2021.102478] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/19/2021] [Accepted: 08/03/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Due to an increased elimination of reactive oxygen species (ROS), in particular hydrogen peroxide (H2O2), overexpression of glutathione peroxidase 1 (GPX1) can lead to an attenuation of apoptosis and development of resistance in cancer cells, thereby promoting tumor cell survival. Consequently, GPX1 inhibitors have the potential to be used in cancer therapy as they support oxidative stress in cancer cells. Similarly, photodynamic therapy (PDT) induces oxidative stress in cancer cells by the formation of ROS upon illumination. Thus, both methods of treatment might act in synergy when used in combination. METHODS To investigate this hypothesis, combinations of the known GPX1 inhibitors 9-chloro-6-ethyl-6H-[1,2,3,4,5]pentathiepino[6,7-b]indole (CEPI) or mercaptosuccinic acid (MSA) with PDT induced by the photosensitizer (PS) temoporfin (5,10,15,20-tetra(m-hydroxyphenyl)chlorin, mTHPC) were studied in vitro. This new combinatory approach was intended to accumulate ROS formed during PDT via blockage of GPX1-catalyzed H2O2 degradation, and thus to enhance PDT-induced phototoxicity. Five human cancer cell lines from tumor origins treatable with PDT were utilized to investigate ROS generation, apoptosis induction, and cell cycle distribution. RESULTS Synergy was identified with both GPX1 inhibitors, but not in all cell lines. ROS levels were increased after combined treatment with mTHPC and CEPI, but not MSA, in some cell lines, indicating that oxidative stress and ROS accumulation were enhanced by CEPI. Surprisingly, enhanced apoptosis induction was also observed with MSA afterwards, suggesting that other pathways contributed to the initiation of apoptosis. Cell cycle analysis confirmed apoptosis induction via the detection of DNA fragmentation. CONCLUSION A combination of GPX1 inhibitors with mTHPC-PDT has the potential to generate synergistic effects and to increase overall phototoxicity, but the success of this combination approach was dependent on cancer type, and even antagonistic effects can occur.
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14
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Lu J, Jiang Z, Ren J, Zhang W, Li P, Chen Z, Zhang W, Wang H, Tang B. One-Pot Synthesis of Multifunctional Carbon-Based Nanoparticle-Supported Dispersed Cu 2+ Disrupts Redox Homeostasis to Enhance CDT. Angew Chem Int Ed Engl 2021; 61:e202114373. [PMID: 34811855 DOI: 10.1002/anie.202114373] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Indexed: 12/11/2022]
Abstract
In chemodynamic therapy (CDT), the levels of reactive oxygen species (ROS) production plays an important role for evaluating the therapeutic efficacy. However, the high levels of glutathione (GSH) in tumor cells consume the ROS, directly reducing the therapeutic efficiency. Herein, we synthesized carbon-based nanoparticle (Cu-cys CBNPs) using one-pot strategy, which consume GSH via redox reactions to produce Cu+ that catalyze H2 O2 to produce . OH, thus the ROS level was observably increased through this synergistic effect. In vivo experiments further revealed that Cu-cys CBNPs could effectively inhibit tumor growth. Additionally, Cu-cys CBNPs can affect the activity of some protein sulfhydryl groups in cells, which was assessed by rdTOP-ABPP assay. In general, this study not only provides a potential CDT drug, but also provides a strategy for one-pot synthesis of multifunctional nanomaterials.
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Affiliation(s)
- Jun Lu
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Zhongyao Jiang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Jie Ren
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Wei Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Ping Li
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Zhenzhen Chen
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Wen Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Hui Wang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China
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15
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Upadhyay A, Kumar Jha R, Batabyal M, Dutta T, Koner AL, Kumar S. Janus -faced oxidant and antioxidant profiles of organo diselenides. Dalton Trans 2021; 50:14576-14594. [PMID: 34590653 DOI: 10.1039/d1dt01565f] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
To date, organoseleniums are pre-eminent for peroxide decomposition and radical quenching antioxidant activities. On the contrary, here, a series of Janus-faced aminophenolic diselenides have been prepared from substituted 2-iodoaniline and selenium powder using copper-catalyzed methodology. Subsequently, condensation with substituted salicylaldehyde afforded the Schiff base, which on reduction, yielded the desired substituted aminophenolic diselenides in 72%-88% yields. The generation of reactive oxygen species (ROS) from oxygen gas by the synthesized aminophenolic diselenides was studied by analyzing the oxidation of dichlorofluorescein diacetate (DCFDA) dye and para-nitro-thiophenol by fluorescence and UV-Visible spectroscopic methods. Furthermore, density functional theory calculations and crystal structure analysis revealed the role of functional amine and hydroxyl sites present in the Janus-faced organoselenium catalyst for the activation of molecular oxygen, where NH and phenolic groups bring the oxygen molecule close to the catalyst by N-H⋯O and O-H⋯O intermolecular interactions. Additionally, these functionalities stabilize the selenium-centered radical in the formed transition states. Antioxidant activities of the synthesized diselenides have been explored as the catalyst for the decomposition of hydrogen peroxide using benzenethiol sacrificial co-reductant by a well-established thiol assay. Radical quenching antioxidant activity was studied by the quenching of DPPH radicals at 516 nm by UV-Visible spectroscopy. The structure activity correlation suggests that the electron-rich phenol and electron-rich and sterically hindered selenium center enhance the oxidizing property of the aminophenolic diselenides. Janus-faced diselenides were also evaluated for their cytotoxic effect on HeLa cancer cells via MTT assay, which suggests that the compounds are effective at 15-18 μM concentration against cancer cells. Moreover, the combination with therapeutic anticancer drugs Erlotinib and Doxorubicin showed promising cytotoxicity at the nanomolar concentration (8-28 nM), which is sufficient to suppress the growth of the cancer cells.
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Affiliation(s)
- Aditya Upadhyay
- Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bhauri By-pass Road, Bhopal 462066, Madhya Pradesh, India.
| | - Raushan Kumar Jha
- Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bhauri By-pass Road, Bhopal 462066, Madhya Pradesh, India.
| | - Monojit Batabyal
- Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bhauri By-pass Road, Bhopal 462066, Madhya Pradesh, India.
| | - Tanoy Dutta
- Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bhauri By-pass Road, Bhopal 462066, Madhya Pradesh, India.
| | - Apurba Lal Koner
- Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bhauri By-pass Road, Bhopal 462066, Madhya Pradesh, India.
| | - Sangit Kumar
- Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bhauri By-pass Road, Bhopal 462066, Madhya Pradesh, India.
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16
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Zheng YW, Miao XY, Xiong L, Chen B, Kong FH, Zhou JJ, Liu ZT, Wen Y, Zhang ZJ, Zou H. Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT. Front Pharmacol 2021; 12:723488. [PMID: 34483935 PMCID: PMC8414975 DOI: 10.3389/fphar.2021.723488] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/27/2021] [Indexed: 01/17/2023] Open
Abstract
Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.
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Affiliation(s)
| | | | | | | | | | | | | | - Yu Wen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Zi-Jian Zhang
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Heng Zou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
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17
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Fan C, Zhai S, Hu W, Chi S, Song D, Liu Z. Gold nanoclusters as a GSH activated mitochondrial targeting photosensitizer for efficient treatment of malignant tumors. RSC Adv 2021; 11:21384-21389. [PMID: 35478781 PMCID: PMC9034094 DOI: 10.1039/d1ra03469c] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/03/2021] [Indexed: 01/09/2023] Open
Abstract
Gold nanoclusters (Au NCs), which have the characteristics of small size, near infrared (NIR) absorption and long triplet excited lifetime, have been used as a new type of photosensitizer for deep tissue photodynamic therapy (PDT). However, the therapeutic efficiency of the nano-system based on Au NCs still needs to be improved. Herein, we proposed a strategy using Mito-Au25@MnO2 nanocomposites to achieve enhanced PDT. Au25(Capt)18− nanoclusters were applied as photosensitizers and further modified with peptides to target mitochondrial and MnO2 nanosheets to consume glutathione (GSH). In the presence of GSH, Mito-Au25@MnO2 dis-integrated and Mito-Au25 nanoparticles realized accurate mitochondrial targeting. Under the irradiation of 808 nm light, the nanocomposite ensured highly efficient PDT both in vitro and in vivo via oxidation pressure elevation and mitochondrial targeting in cancer cells. This is the first example of mitochondrial targeting Au NCs capable of improving the efficiency of photodynamic therapy. Mito-Au25@MnO2 can be activated by consuming GSH and elevating oxidation pressure in cancer cells.![]()
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Affiliation(s)
- Chen Fan
- Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University Wuhan 430072 China
| | - Shuyang Zhai
- Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University Wuhan 430072 China
| | - Wei Hu
- Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University Wuhan 430072 China
| | - Siyu Chi
- Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University Wuhan 430072 China
| | - Dan Song
- Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University Wuhan 430072 China
| | - Zhihong Liu
- Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University Wuhan 430072 China
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18
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Cheng X, Xu HD, Ran HH, Liang G, Wu FG. Glutathione-Depleting Nanomedicines for Synergistic Cancer Therapy. ACS NANO 2021; 15:8039-8068. [PMID: 33974797 DOI: 10.1021/acsnano.1c00498] [Citation(s) in RCA: 212] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Propelled by the rapid development of nanotechnology, GSH-depleting agents can be readily constructed into anticancer nanomedicines, which have shown a steep rise over the past decade. Here, we review the common GSH-depleting nanomedicines which have been widely applied in synergistic cancer treatments in recent years. Some current challenges and future perspectives for GSH depletion-based cancer therapies are also presented. With the understanding of the structure-property relationship and action mechanisms of these biomaterials, we hope that the GSH-depleting nanotechnology will be further developed to realize more effective disease treatments and even achieve successful clinical translations.
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Affiliation(s)
- Xiaotong Cheng
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P.R. China
| | - Hai-Dong Xu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P.R. China
| | - Huan-Huan Ran
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P.R. China
| | - Gaolin Liang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P.R. China
| | - Fu-Gen Wu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P.R. China
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19
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Xiong Y, Xiao C, Li Z, Yang X. Engineering nanomedicine for glutathione depletion-augmented cancer therapy. Chem Soc Rev 2021; 50:6013-6041. [PMID: 34027953 DOI: 10.1039/d0cs00718h] [Citation(s) in RCA: 382] [Impact Index Per Article: 95.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Glutathione (GSH), the main redox buffer, has long been recognized as a pivotal modulator of tumor initiation, progression and metastasis. It is also implicated in the resistance of platinum-based chemotherapy and radiation therapy. Therefore, depleting intracellular GSH was considered a potent solution to combating cancer. However, reducing GSH within cancer cells alone always failed to yield desirable therapeutic effects. In this regard, the convergence of GSH-scavenging agents with therapeutic drugs has thus been pursued in clinical practice. Unfortunately, the therapeutic outcomes are still unsatisfactory due to untargeted drug delivery. Advanced nanomedicine of synergistic GSH depletion and cancer treatment has attracted tremendous interest because they promise to deliver superior therapeutic benefits while alleviating life-threatening side effects. In the past five years, the authors and others have demonstrated that numerous nanomedicines, by simultaneously delivering GSH-depleting agents and therapeutic components, boost not only traditional chemotherapy and radiotherapy but also multifarious emerging treatment modalities, including photodynamic therapy, sonodynamic therapy, chemodynamic therapy, ferroptosis, and immunotherapy, to name a few, and achieved decent treatment outcomes in a large number of rodent tumor models. In this review, we summarize the most recent progress in engineering nanomedicine for GSH depletion-enhanced cancer therapies. Biosynthesis of GSH and various types of GSH-consuming strategies will be briefly introduced. The challenges and perspectives of leveraging nanomedicine for GSH consumption-augmented cancer therapies will be discussed at the end.
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Affiliation(s)
- Yuxuan Xiong
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.
| | - Chen Xiao
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.
| | - Zifu Li
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. and Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and Wuhan Institute of Biotechnology, High Tech Road 666, East Lake high tech Zone, Wuhan, 430040, P. R. China
| | - Xiangliang Yang
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. and Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and GBA Research Innovation Institute for Nanotechnology, Guangdong, 510530, P. R. China
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20
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Ke L, Wei F, Liao X, Rees TW, Kuang S, Liu Z, Chen Y, Ji L, Chao H. Nano-assembly of ruthenium(II) photosensitizers for endogenous glutathione depletion and enhanced two-photon photodynamic therapy. NANOSCALE 2021; 13:7590-7599. [PMID: 33884385 DOI: 10.1039/d1nr00773d] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Photodynamic therapy (PDT) is a promising noninvasive cancer treatment. PDT in the clinic faces several hurdles due to the unique tumor environment, a feature of which is high levels of glutathione (GSH). An excess amount of GSH consumes reactive oxygen species (ROS) generated by photosensitizers (PSs), reducing PDT efficiency. Herein, nano-photosensitizers (RuS1 NPs and RuS2 NPs) are reported. These consist of ruthenium complexes joined by disulfide bonds forming GSH sensitive polymer nanoparticles. The NPs achieve enhanced uptake compared to their constituent monomers. Inside cancer cells, high levels of GSH break the S-S bonds releasing PS molecules in the cell. The level of GSH is also then reduced leading to excellent PDT activity. Furthermore, RuS2 NPs functionalized with tumor targeting hyaluronic acid (HA@RuS2 NPs) assessed in vivo were highly effective with minimal side effects. To the best of our knowledge, RuS NPs are the first metal complex-based nano-assembled photosensitizers which exhibit enhanced specificity and consume endogenous GSH simultaneously, thus achieving excellent two-photon PDT efficiency in vitro and in vivo.
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Affiliation(s)
- Libing Ke
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Fangmian Wei
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Xinxing Liao
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Thomas W Rees
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Shi Kuang
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Zhou Liu
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Yu Chen
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Liangnian Ji
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Hui Chao
- MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.
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21
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Daouk J, Iltis M, Dhaini B, Béchet D, Arnoux P, Rocchi P, Delconte A, Habermeyer B, Lux F, Frochot C, Tillement O, Barberi-Heyob M, Schohn H. Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy. Pharmaceuticals (Basel) 2021; 14:ph14050396. [PMID: 33922073 PMCID: PMC8143523 DOI: 10.3390/ph14050396] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/18/2021] [Accepted: 04/19/2021] [Indexed: 01/10/2023] Open
Abstract
X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a nanoscintillator and 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenyl porphyrin (P1) as a photosensitizer (AGuIX@Tb-P1). The synthesis was based on the AGuIX@ platform design. AGuIX@Tb-P1 was characterised for its photo-physical and physico-chemical properties. The effect of the nanoparticles was studied using human glioblastoma U-251 MG cells and was compared to treatment with AGuIX@ nanoparticles doped with Gadolinium (Gd) and P1 (AGuIX@Gd-P1). We demonstrated that the AGuIX@Tb-P1 design was consistent with X-ray photon energy transfer from Terbium to P1. Both nanoparticles had similar dark cytotoxicity and they were absorbed in a similar rate within the cells. Pre-treated cells exposure to X-rays was related to reactive species production. Using clonogenic assays, establishment of survival curves allowed discrimination of the impact of radiation treatment from X-ray-induced photodynamic effect. We showed that cell growth arrest was increased (35%-increase) when cells were treated with AGuIX@Tb-P1 compared to the nanoparticle doped with Gd.
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Affiliation(s)
- Joël Daouk
- Department of Biology, Signals and Systems in Cancer and Neuroscience, UMR 7039 Research Center for Automatic Control (CRAN), Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (J.D.); (M.I.); (D.B.); (A.D.); (H.S.)
| | - Mathilde Iltis
- Department of Biology, Signals and Systems in Cancer and Neuroscience, UMR 7039 Research Center for Automatic Control (CRAN), Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (J.D.); (M.I.); (D.B.); (A.D.); (H.S.)
| | - Batoul Dhaini
- Reactions and Chemical Engineering Laboratory (LRGP), UMR 7274, Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (B.D.); (P.A.); (C.F.)
| | - Denise Béchet
- Department of Biology, Signals and Systems in Cancer and Neuroscience, UMR 7039 Research Center for Automatic Control (CRAN), Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (J.D.); (M.I.); (D.B.); (A.D.); (H.S.)
| | - Philippe Arnoux
- Reactions and Chemical Engineering Laboratory (LRGP), UMR 7274, Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (B.D.); (P.A.); (C.F.)
| | - Paul Rocchi
- Light Matter Institute, UMR-5306, Université de Lyon–French National Scientific Research Center (CNRS), F-69000 Lyon, France; (P.R.); (F.L.); (O.T.)
| | - Alain Delconte
- Department of Biology, Signals and Systems in Cancer and Neuroscience, UMR 7039 Research Center for Automatic Control (CRAN), Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (J.D.); (M.I.); (D.B.); (A.D.); (H.S.)
| | | | - François Lux
- Light Matter Institute, UMR-5306, Université de Lyon–French National Scientific Research Center (CNRS), F-69000 Lyon, France; (P.R.); (F.L.); (O.T.)
| | - Céline Frochot
- Reactions and Chemical Engineering Laboratory (LRGP), UMR 7274, Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (B.D.); (P.A.); (C.F.)
| | - Olivier Tillement
- Light Matter Institute, UMR-5306, Université de Lyon–French National Scientific Research Center (CNRS), F-69000 Lyon, France; (P.R.); (F.L.); (O.T.)
| | - Muriel Barberi-Heyob
- Department of Biology, Signals and Systems in Cancer and Neuroscience, UMR 7039 Research Center for Automatic Control (CRAN), Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (J.D.); (M.I.); (D.B.); (A.D.); (H.S.)
- Correspondence: ; Tel.: +33-(0)3-72-74-61-14
| | - Hervé Schohn
- Department of Biology, Signals and Systems in Cancer and Neuroscience, UMR 7039 Research Center for Automatic Control (CRAN), Université de Lorraine–French National Scientific Research Center (CNRS), F-54000 Nancy, France; (J.D.); (M.I.); (D.B.); (A.D.); (H.S.)
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22
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Yuan J, Peng R, Su D, Zhang X, Zhao H, Zhuang X, Chen M, Zhang X, Yuan L. Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy. Theranostics 2021; 11:3502-3511. [PMID: 33537100 PMCID: PMC7847693 DOI: 10.7150/thno.55014] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/17/2020] [Indexed: 11/29/2022] Open
Abstract
Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (1O2), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of 1O2 on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs.
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Affiliation(s)
- Jie Yuan
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R China
| | - Rong Peng
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R China
| | - Dongdong Su
- Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124, P. R. China
| | - Xingxing Zhang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R China
| | - Hepeng Zhao
- College of Physics and Microelectronics Science, Hunan University, Changsha 410082, P. R China
| | - Xiujuan Zhuang
- College of Physics and Microelectronics Science, Hunan University, Changsha 410082, P. R China
| | - Mei Chen
- College of Materials Science and Engineering, Hunan University, Changsha 410082, P. R China
| | - Xiaobing Zhang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R China
| | - Lin Yuan
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R China
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23
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Ming L, Cheng K, Chen Y, Yang R, Chen D. Enhancement of tumor lethality of ROS in photodynamic therapy. Cancer Med 2021; 10:257-268. [PMID: 33141513 PMCID: PMC7826450 DOI: 10.1002/cam4.3592] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/10/2020] [Accepted: 10/12/2020] [Indexed: 12/18/2022] Open
Abstract
In the process of photodynamic therapy (PDT) treatment of tumors, reactive oxygen species (ROS) plays a key role in destroying tumor tissues. However, traditional PDT often has limited ROS killing capacity due to hypoxia in the tumor microenvironment (TME) or obstruction by the ROS defense system, resulting in poor efficacy. Therefore, enhancing the killing effect of ROS on tumors is the core of enhancing the anti-tumor effect of PDT. In recent years, many studies have developed a series of strategies to enhance the ability of ROS to kill tumors in view of the limitations of the TME on PDT. This article summarizes the commonly used or innovative strategies in recent years, including not only frequently used methods for hypoxia in the TME but also innovative strategies to inhibit the ROS defense system.
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Affiliation(s)
- Lan Ming
- Research Institute for Reproductive Health and Genetic DiseasesThe Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxiChina
| | - Kai Cheng
- Research Institute for Reproductive Health and Genetic DiseasesThe Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxiChina
| | - Yu Chen
- Research Institute for Reproductive Health and Genetic DiseasesThe Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxiChina
| | - Rui Yang
- Research Institute for Reproductive Health and Genetic DiseasesThe Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxiChina
| | - Daozhen Chen
- Research Institute for Reproductive Health and Genetic DiseasesThe Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxiChina
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24
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Ibarra LE, Vilchez ML, Caverzán MD, Milla Sanabria LN. Understanding the glioblastoma tumor biology to optimize photodynamic therapy: From molecular to cellular events. J Neurosci Res 2020; 99:1024-1047. [PMID: 33370846 DOI: 10.1002/jnr.24776] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 11/29/2020] [Indexed: 12/19/2022]
Abstract
Photodynamic therapy (PDT) has recently gained attention as an alternative treatment of malignant gliomas. Glioblastoma (GBM) is the most prevalent within tumors of the central nervous system (CNS). Conventional treatments for this CNS tumor include surgery, radiation, and chemotherapy. Surgery is still being considered as the treatment of choice. Even so, the poor prognosis and/or recurrence of the disease after applying any of these treatments highlight the urgency of exploring new therapies and/or improving existing ones to achieve the definitive eradication of tumor masses and remaining cells. PDT is a therapeutic modality that involves the destruction of tumor cells by reactive oxygen species induced by light, which were previously treated with a photosensitizing agent. However, in recent years, its experimental application has expanded to other effects that could improve overall performance against GBM. In the current review, we revisit the main advances of PDT for GBM management and also, the recent mechanistic insights about cellular and molecular aspects related to tumoral resistance to PDT of GBM.
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Affiliation(s)
- Luis Exequiel Ibarra
- Instituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Río Cuarto, Argentina.,Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, UNRC, Río Cuarto, Argentina
| | - María Laura Vilchez
- Instituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Río Cuarto, Argentina.,Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, UNRC, Río Cuarto, Argentina
| | - Matías Daniel Caverzán
- Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, UNRC, Río Cuarto, Argentina
| | - Laura Natalia Milla Sanabria
- Instituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Río Cuarto, Argentina.,Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, UNRC, Río Cuarto, Argentina
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25
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Chakraborty I, Hossain CM, Basak P. Synthesis and characterization of ester-diol based polyurethane: a potentiality check for hypopharyngeal tissue engineering application. Biomed Eng Lett 2020; 11:25-37. [PMID: 33747601 DOI: 10.1007/s13534-020-00180-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 10/22/2020] [Accepted: 11/16/2020] [Indexed: 10/22/2022] Open
Abstract
Abstract Hypopharyngeal tissue engineering is increasing rapidly in this developing world. Tissue damage or loss needs the replacement by another biological or synthesized membrane using tissue engineering. Tissue engineering research is emerging to provide an effective solution for damaged tissue replacement. Polyurethane in tissue engineering has successfully been used to repair and restore the function of damaged tissues. In this context, Can polyurethane be a useful material to deal with hypopharyngeal tissue defects? To explore this, here ester diol based polyurethane (PU) was synthesized in two steps: firstly, polyethylene glycol 400 (PEG 400) was reacted with lactic acid to prepare ester diol, and then it was polymerized with hexamethylene diisocyanate. The physical, mechanical, and biological testing was done to testify the characterization of the membrane. The morphology of the synthesized membrane was investigated by using field emission scanning electron microscopy. Functional groups of the obtained membrane were characterized by fourier transform infrared spectroscopy spectroscopy. Several tests were performed to check the in vitro and in vivo biocompatibility of the membrane. A highly connected homogeneous network was obtained due to the appropriate orientation of a hard segment and soft segment in the synthesized membrane. Mechanical property analysis indicates the membrane has a strength of 5.15 MPa and strain 124%. The membrane showed high hemocompatibility, no cytotoxicity on peripheral blood mononuclear cell, and susceptible to degradation in simulated body fluid solution. Antimicrobial activity assessment has shown promising results against clinically significant bacteria. Primary hypopharyngeal cell growth on the PU membrane revealed the cytocompatibility and subcutaneous implantation on the back of Wistar rats were given in vivo biocompatibility of the membrane. Therefore, the synthesized material can be considered as a potential candidate for a hypopharyngeal tissue engineering application. Graphic abstract
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Affiliation(s)
- Imon Chakraborty
- School of Bioscience and Engineering, Jadavpur University, Kolkata, India
| | | | - Piyali Basak
- School of Bioscience and Engineering, Jadavpur University, Kolkata, India
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26
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Zhu J, Xiao T, Zhang J, Che H, Shi Y, Shi X, van Hest JCM. Surface-Charge-Switchable Nanoclusters for Magnetic Resonance Imaging-Guided and Glutathione Depletion-Enhanced Photodynamic Therapy. ACS NANO 2020; 14:11225-11237. [PMID: 32809803 PMCID: PMC7513467 DOI: 10.1021/acsnano.0c03080] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
Photodynamic therapy (PDT) is an effective noninvasive therapeutic method that employs photosensitizers (PSs) converting oxygen to highly cytotoxic singlet oxygen (1O2) under light irradiation. The conventional PDT efficacy is, however, compromised by the nonspecific delivery of PSs to tumor tissue, the hypoxic tumor microenvironment, and the reduction of generated 1O2 by the intracellular antioxidant glutathione (GSH). Herein, an intelligent multifunctional synergistic nanoplatform (CMGCC) for T1-weighted magnetic resonance (MR) imaging-guided enhanced PDT is presented, which consists of nanoparticles composed of catalase (CAT) and manganese dioxide (MnO2) that are integrated within chlorin-e6-modified glycol chitosan (GC) polymeric micelles. In this system, (1) GC polymers with pH-sensitive surface charge switchability from neutral to positive could improve the PS accumulation within the tumor region, (2) CAT could effectively reoxygenate the hypoxic tumor via catalyzing endogenous hydrogen peroxide to O2, and (3) MnO2 could consume the intracellular GSH while simultaneously producing Mn2+ as a contrast agent for T1-weighted MR imaging. The CMGCC particles possess uniform size distribution, well-defined structure, favorable enzyme activity, and superior 1O2 generation ability. Both in vitro and in vivo experiments demonstrate that the CMGCC exhibit significantly enhanced PDT efficacy toward HeLa cells and subcutaneous HeLa tumors. Our study thereby demonstrates this to be a promising synergistic theranostic nanoplatform with highly efficient PDT performance for cancer therapy.
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Affiliation(s)
- Jianzhi Zhu
- Bio-Organic
Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
- State
Key Laboratory for Modification of Chemical Fibers and Polymer Materials,
International Joint Laboratory for Advanced Fiber and Low-dimension
Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People’s Republic of China
| | - Tingting Xiao
- State
Key Laboratory for Modification of Chemical Fibers and Polymer Materials,
International Joint Laboratory for Advanced Fiber and Low-dimension
Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People’s Republic of China
| | - Jiulong Zhang
- Department
of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People’s Republic
of China
| | - Hailong Che
- Bio-Organic
Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
| | - Yuxin Shi
- Department
of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People’s Republic
of China
| | - Xiangyang Shi
- State
Key Laboratory for Modification of Chemical Fibers and Polymer Materials,
International Joint Laboratory for Advanced Fiber and Low-dimension
Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People’s Republic of China
| | - Jan C. M. van Hest
- Bio-Organic
Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
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27
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Li S, Bi B, Luo G, Zhan J, Zhang R, Li J, Chen N, Huang J, Xue J, Xu G. A phase Ι study to evaluate the application of photocyanine using pharmacokinetic and pharmacodynamic analysis in patients with malignancy. Cancer Chemother Pharmacol 2020; 86:267-276. [PMID: 32710147 DOI: 10.1007/s00280-020-04096-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 06/03/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Photodynamic therapy (PDT) schedules are based on sensitiser dose, light dose, and drug-light interval. The aim of the phase Ι study was to choose optimal dose and drug-light interval for PDT with photocyanine using pharmacokinetics (PK) and pharmacodynamics (PD). METHODS Twenty-eight cancer patients were enrolled. In trial A, 12 patients received one of four ascending doses of photocyanine intravenously 24 h prior to 180-270 J/cm2 illumination. 0.2 mg/kg dose was infused to ten patients 12-48 h prior to 120 J/cm2 illumination in trial B. In trial C, 0.1 mg/kg dose was infused to six patients 6 or 12 h prior to 180-270 J/cm2 illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses. RESULTS Analysis of photocyanine levels of patients indicated that the two-compartment model best fit the data. Simulations showed that the rates of the drug entering tissues and leaving tissues were equal at 8-12 h after injection. Patients experienced pain which was related to photocyanine serum levels, especially with serum levels above 2500 ng/ml. Fewer non-responders were observed at serum levels higher than 1000 ng/ml for illumination at least 12 h after administration. CONCLUSION It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm2 illumination about 20-30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.
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Affiliation(s)
- Su Li
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.,Department of Clinical Trial Center, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China
| | - Bingtian Bi
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.,Department of Clinical Trial Center, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China
| | - Guangyu Luo
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.,Department of Endoscopy, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China
| | - Jing Zhan
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.,Department of Clinical Trial Center, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China
| | - Rong Zhang
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.,Department of Endoscopy, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China
| | - Jibin Li
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.,Department of Clinical Trial Center, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China
| | - Naisheng Chen
- College of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China
| | - Jinling Huang
- College of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China
| | - Jinping Xue
- College of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China.
| | - Guoliang Xu
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. .,Department of Endoscopy, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
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Chen Y, Cong H, Shen Y, Yu B. Biomedical application of manganese dioxide nanomaterials. NANOTECHNOLOGY 2020; 31:202001. [PMID: 31978932 DOI: 10.1088/1361-6528/ab6fe1] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Manganese dioxide nanomaterial is a new type of inorganic nanomaterial offering numerous advantages: simple preparation, low cost, and environmental friendliness. This review summarizes the traditional and novel synthetic methods for manganese dioxide nanomaterials and mainly discusses their potential in biomedical applications. Manganese dioxide nanomaterials are mainly used as drug carriers in tumor therapy. In recent years, the construction of multifunctional nano-platforms using manganese dioxide has gradually improved. The main mechanism is that manganese dioxide nanomaterials can combine with reactive oxygen species in the tumor microenvironment to alleviate tumor hypoxia. Manganese dioxide has also been used to quench fluorescent carbon dots in fluorescent probes. Based on the oxidation ability and catalytic activity of MnO2, MnO2 nanosheets are widely used to build biosensors. New research shows that manganese dioxide nanomaterials also have great potential in gene therapy and nuclear magnetic imaging.
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Affiliation(s)
- Yang Chen
- Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, People's Republic of China
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Chen J, Fan T, Xie Z, Zeng Q, Xue P, Zheng T, Chen Y, Luo X, Zhang H. Advances in nanomaterials for photodynamic therapy applications: Status and challenges. Biomaterials 2020; 237:119827. [PMID: 32036302 DOI: 10.1016/j.biomaterials.2020.119827] [Citation(s) in RCA: 423] [Impact Index Per Article: 84.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/13/2020] [Accepted: 01/25/2020] [Indexed: 12/24/2022]
Abstract
Photodynamic therapy (PDT), as a non-invasive therapeutic modality that is alternative to radiotherapy and chemotherapy, is extensively investigated for cancer treatments. Although conventional organic photosensitizers (PSs) are still widely used and have achieved great progresses in PDT, the disadvantages such as hydrophobicity, poor stability within PDT environment and low cell/tissue specificity largely limit their clinical applications. Consequently, nano-agents with promising physicochemical and optical properties have emerged as an attractive alternative to overcome these drawbacks of traditional PSs. Herein, the up-to-date advances in the fabrication and fascinating applications of various nanomaterials in PDT have been summarized, including various types of nanoparticles, carbon-based nanomaterials, and two-dimensional nanomaterials, etc. In addition, the current challenges for the clinical use of PDT, and the corresponding strategies to address these issues, as well as future perspectives on further improvement of PDT have also been discussed.
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Affiliation(s)
- Jianming Chen
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Taojian Fan
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Zhongjian Xie
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Qiqiao Zeng
- Department of Ophthalmology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen City, Guangdong Province, 518020, PR China
| | - Ping Xue
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China
| | - Tingting Zheng
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, 518036, PR China
| | - Yun Chen
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, 518036, PR China
| | - Xiaoling Luo
- Department of Ophthalmology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen City, Guangdong Province, 518020, PR China.
| | - Han Zhang
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China.
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Lee HM, Kim DH, Lee HL, Cha B, Kang DH, Jeong YIL. Synergistic effect of buthionine sulfoximine on the chlorin e6-based photodynamic treatment of cancer cells. Arch Pharm Res 2019; 42:990-999. [DOI: 10.1007/s12272-019-01179-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 08/10/2019] [Indexed: 11/28/2022]
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Donohoe C, Senge MO, Arnaut LG, Gomes-da-Silva LC. Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity. Biochim Biophys Acta Rev Cancer 2019; 1872:188308. [PMID: 31401103 DOI: 10.1016/j.bbcan.2019.07.003] [Citation(s) in RCA: 237] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 07/25/2019] [Accepted: 07/25/2019] [Indexed: 01/11/2023]
Abstract
Photodynamic therapy is a promising approach for cancer treatment that relies on the administration of a photosensitizer followed by tumor illumination. The generated oxidative stress may activate multiple mechanisms of cell death which are counteracted by cells through adaptive stress responses that target homeostasis rescue. The present renaissance of PDT was leveraged by the acknowledgment that this therapy has an immediate impact locally, in the illumination volume, but that subsequently it may also elicit immune responses with systemic impact. The investigation of the mechanisms of cell death under the oxidative stress of PDT is of paramount importance to understand how the immune system is activated and, ultimately, to make PDT a more appealing/relevant therapeutic option.
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Affiliation(s)
- Claire Donohoe
- CQC, Coimbra Chemistry Center, University of Coimbra, Portugal; Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St. James's Hospital, Dublin 8, Ireland
| | - Mathias O Senge
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St. James's Hospital, Dublin 8, Ireland
| | - Luís G Arnaut
- CQC, Coimbra Chemistry Center, University of Coimbra, Portugal
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32
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Hu H, Chen J, Yang H, Huang X, Wu H, Wu Y, Li F, Yi Y, Xiao C, Li Y, Tang Y, Li Z, Zhang B, Yang X. Potentiating photodynamic therapy of ICG-loaded nanoparticles by depleting GSH with PEITC. NANOSCALE 2019; 11:6384-6393. [PMID: 30888375 DOI: 10.1039/c9nr01306g] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Photodynamic therapy (PDT) is a clinically approved cancer treatment which utilizes reactive oxygen species (ROS) to eradicate cancer cells. But the high concentration of GSH inside tumor cells can neutralize the generated ROS during PDT, resulting in an insufficient therapeutic effect. To address this issue, we combined ICG-loaded nanoparticles with PEITC for potent PDT. ICG encapsulated in novel hydroxyethyl starch-oleic acid conjugate (HES-OA) nanoparticles (∼50 nm) exhibited excellent stability and efficient singlet oxygen generation under laser irradiation, promoted cellular uptake, and enhanced tumor accumulation, whilst PEITC depleted intracellular GSH significantly. As a result, PDT based on ICG-loaded NPs combined with PEITC synergistically suppressed cancer cells both in vitro and in vivo. Potentiating ICG-loaded NPs with PEITC represents a novel and efficient strategy to enhance PDT efficacy.
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Affiliation(s)
- Hang Hu
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China
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Gu Z, Zhu S, Yan L, Zhao F, Zhao Y. Graphene-Based Smart Platforms for Combined Cancer Therapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2019; 31:e1800662. [PMID: 30039878 DOI: 10.1002/adma.201800662] [Citation(s) in RCA: 195] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/25/2018] [Indexed: 06/08/2023]
Abstract
The extensive research of graphene and its derivatives in biomedical applications during the past few years has witnessed its significance in the field of nanomedicine. Starting from simple drug delivery systems, the application of graphene and its derivatives has been extended to a versatile platform of multiple therapeutic modalities, including photothermal therapy, photodynamic therapy, magnetic hyperthermia therapy, and sonodynamic therapy. In addition to monotherapy, graphene-based materials are widely applied in combined therapies for enhanced anticancer activity and reduced side effects. In particular, graphene-based materials are often designed and fabricated as "smart" platforms for stimuli-responsive nanocarriers, whose therapeutic effects can be activated by the tumor microenvironment, such as acidic pH and elevated glutathione (termed as "endogenous stimuli"), or light, magnetic, or ultrasonic stimuli (termed as "exogenous stimuli"). Herein, the recent advances of smart graphene platforms for combined therapy applications are presented, starting with the principle for the design of graphene-based smart platforms in combined therapy applications. Next, recent advances of combined therapies contributed by graphene-based materials, including chemotherapy-based, photothermal-therapy-based, and ultrasound-therapy-based synergistic therapy, are outlined. In addition, current challenges and future prospects regarding this promising field are discussed.
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Affiliation(s)
- Zhanjun Gu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China
- College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Shuang Zhu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China
| | - Liang Yan
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China
| | - Feng Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China
| | - Yuliang Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China
- College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing, 100190, China
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Adigbli DK, Pye H, Seebaluck J, Loizidou M, MacRobert AJ. The intracellular redox environment modulates the cytotoxic efficacy of single and combination chemotherapy in breast cancer cells using photochemical internalisation. RSC Adv 2019; 9:25861-25874. [PMID: 35530074 PMCID: PMC9070005 DOI: 10.1039/c9ra04430b] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 08/09/2019] [Indexed: 12/27/2022] Open
Abstract
The redox environment modulates photochemical internalization of an entrapped cytotoxic agent. Administration of light depicted by jagged arrow.
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Affiliation(s)
- Derick K. Adigbli
- Division of Surgery and Interventional Science
- University College London
- London
- UK
| | - Hayley Pye
- Division of Surgery and Interventional Science
- University College London
- London
- UK
| | - Jason Seebaluck
- Division of Surgery and Interventional Science
- University College London
- London
- UK
| | - Marilena Loizidou
- Division of Surgery and Interventional Science
- University College London
- London
- UK
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35
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Zhang H, Liu K, Li S, Xin X, Yuan S, Ma G, Yan X. Self-Assembled Minimalist Multifunctional Theranostic Nanoplatform for Magnetic Resonance Imaging-Guided Tumor Photodynamic Therapy. ACS NANO 2018; 12:8266-8276. [PMID: 30091901 DOI: 10.1021/acsnano.8b03529] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Minimalist multifunctional platforms for delivering diagnostic and therapeutic agents effectively and safely into tumor sites are highly desired in nanomedicine. Herein, we describe the fabrication of a supramolecular nanoplatform via the amphiphilic amino acid (9-fluorenylmethyloxycarbonyl-l-leucine, Fmoc-l-L)-modulated self-assembly of a magnetic resonance imaging (MRI) contrast agent (ionic manganese, Mn2+) and photosensitive drug (chlorin e6, Ce6). Coordination drives the coassembly of Fmoc-l-L and Mn2+ to generate a nanoscale supramolecular network to adaptively encapsulate Ce6. The obtained biometal-organic nanoparticles exhibit a high drug loading capability, inherent good biocompatibility, robust stability, and smart disassembly in response to glutathione (GSH). The cooperative assembly of the multiple components is synchronously dynamic in nature and enables enhanced photodynamic therapy (PDT) to damage tumor cells and tissue by efficiently delivering the photosensitizer and improving the reductive tumor microenvironment via the competitive coordination of GSH with Mn2+. The antitumor effect can also be monitored and evaluated in vivo by MRI through the long-term intracellular biochelation of Mn2+. Therefore, this work presents a one-pot and robust method for the self-assembly of a multifunctional theranostic nanoplatform capable of MRI-guided PDT starting from minimalist biological building blocks.
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Affiliation(s)
- Han Zhang
- Key Lab for Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering , Shandong University , Jinan 250100 , P.R. China
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100190 , P.R. China
| | - Kai Liu
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100190 , P.R. China
- University of Chinese Academy of Sciences , Beijing 100049 , P.R. China
| | - Shukun Li
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100190 , P.R. China
- University of Chinese Academy of Sciences , Beijing 100049 , P.R. China
| | - Xia Xin
- Key Lab for Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering , Shandong University , Jinan 250100 , P.R. China
- National Engineering Technology Research Center for Colloidal Materials , Shandong University , Jinan 250100 , P.R. China
| | - Shiling Yuan
- Key Lab for Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering , Shandong University , Jinan 250100 , P.R. China
| | - Guanghui Ma
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100190 , P.R. China
| | - Xuehai Yan
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100190 , P.R. China
- University of Chinese Academy of Sciences , Beijing 100049 , P.R. China
- Center for Mesoscience, Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100190 , P.R. China
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Wu Q, Wei G, Xu Z, Han J, Xi J, Fan L, Gao L. Mechanistic Insight into the Light-Irradiated Carbon Capsules as an Antibacterial Agent. ACS APPLIED MATERIALS & INTERFACES 2018; 10:25026-25036. [PMID: 29989399 DOI: 10.1021/acsami.8b04932] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Infections caused by bacteria are a growing global challenge for public health as bacteria develop resistance, which will cause the failure of anti-infective treatment eventually. An effective alternative strategy to traditional antibacterial therapy is utilizing reactive oxygen species (ROS) to kill bacteria. Here, we report a simple route to prepare PEGylated nitrogen-doped carbon capsules (PEG-N-CCs) as an antibacterial agent. The PEG-N-CCs can translate near-infrared light (NIR) into heat and produce a high concentration of ROS triggered by NIR irradiation. Both heating and ROS are critical to destroy the outer membranes and rupture cell bodies, causing DNA fragmentation and glutathione oxidation both in Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and their multidrug-resistant strains. Moreover, PEG-N-CCs plus NIR irradiation can efficiently scavenge the existing biofilms and prevent the formation of new biofilms, killing planktonic bacteria as well as those within the biofilm. Our studies prove that the PEG-N-CCs plus NIR irradiation can provide a simple and effective platform for combating bacteria, employing carbon nanomaterials as an antibacterial alternative for treatment of infectious diseases.
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Affiliation(s)
- Qiuwen Wu
- Department of Pharmacology, Institute of Translational Medicine, School of Medicine , Yangzhou University , Yangzhou 225001 , Jiangsu , China
| | - Gen Wei
- Department of Pharmacology, Institute of Translational Medicine, School of Medicine , Yangzhou University , Yangzhou 225001 , Jiangsu , China
| | - Zhuobin Xu
- Department of Pharmacology, Institute of Translational Medicine, School of Medicine , Yangzhou University , Yangzhou 225001 , Jiangsu , China
| | - Jing Han
- Department of Pharmacology, Institute of Translational Medicine, School of Medicine , Yangzhou University , Yangzhou 225001 , Jiangsu , China
| | - Juqun Xi
- Department of Pharmacology, Institute of Translational Medicine, School of Medicine , Yangzhou University , Yangzhou 225001 , Jiangsu , China
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases , Yangzhou 225001 , Jiangsu , China
| | - Lei Fan
- School of Chemistry and Chemical Engineering , Yangzhou University , Yangzhou 225002 , Jiangsu , China
| | - Lizeng Gao
- Department of Pharmacology, Institute of Translational Medicine, School of Medicine , Yangzhou University , Yangzhou 225001 , Jiangsu , China
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Marydasan B, Madhuri B, Cherukommu S, Jose J, Viji M, Karunakaran SC, Chandrashekar TK, Rao KS, Rao CM, Ramaiah D. In Vitro and In Vivo Demonstration of Human-Ovarian-Cancer Necrosis through a Water-Soluble and Near-Infrared-Absorbing Chlorin. J Med Chem 2018; 61:5009-5019. [DOI: 10.1021/acs.jmedchem.8b00460] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Betsy Marydasan
- Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum 695 019, India
| | - Bollapalli Madhuri
- CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500 007, India
| | - Shirisha Cherukommu
- CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500 007, India
| | - Jedy Jose
- CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500 007, India
| | - Mambattakkara Viji
- Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum 695 019, India
| | - Suneesh C. Karunakaran
- Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum 695 019, India
| | | | - Kunchala Sridhar Rao
- Indo-American Cancer Research Foundation (IACRF), Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad 500034, India
| | - Ch. Mohan Rao
- CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500 007, India
| | - Danaboyina Ramaiah
- CSIR-North East Institute of Science and Technology (CSIR-NEIST), Jorhat 785 006, India
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Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with CuII
as the Active Center. Angew Chem Int Ed Engl 2018. [DOI: 10.1002/ange.201710800] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Zhang W, Lu J, Gao X, Li P, Zhang W, Ma Y, Wang H, Tang B. Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with CuII
as the Active Center. Angew Chem Int Ed Engl 2018; 57:4891-4896. [DOI: 10.1002/anie.201710800] [Citation(s) in RCA: 217] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Indexed: 12/18/2022]
Affiliation(s)
- Wei Zhang
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Jun Lu
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Xiaonan Gao
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Ping Li
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Wen Zhang
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Yu Ma
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Hui Wang
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science; Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong; Key Laboratory of Molecular and Nano Probes; Ministry of Education; Institute of Biomedical Sciences; Shandong Normal University; Jinan 250014 P. R. China
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Lund K, Olsen CE, Wong JJW, Olsen PA, Solberg NT, Høgset A, Krauss S, Selbo PK. 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 2017; 36:187. [PMID: 29258566 PMCID: PMC5738190 DOI: 10.1186/s13046-017-0662-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 12/07/2017] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. METHODS 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS2a and to investigate the effect of photodamage of lysosomes. Flow cytometric analysis was performed to investigate uptake of photosensitizer and to assess intracellular ROS levels. Expression and localization of LAMP1 was assessed using RT-qPCR, western blotting, and structured illumination microscopy. MTS viability assay was used to assess the effect of combinations of 5-FU, chloroquine (CQ), and photochemical treatment. Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS2a and anti-CD105-saporin was assessed using microscopy. Lastly, the MTS assay was used to investigate cytotoxic effects of photochemical internalization (PCI) of the anti-CD105-immunotoxin. RESULTS The 5-FUR cell lines display hypersensitivity to PCT, which was linked to increased uptake of TPCS2a, altered lysosomal distribution, lysosomal photodamage and increased expression of the lysosomal marker LAMP-1 in the 5-FUR cells. We show that inhibition of autophagy induced by either chloroquine or lysosomal photodamage increases the sensitivity to 5-FU in the resistant cells. The three 5-FUR sub-clones overexpress Endoglin (CD105). Treatment with the immunotoxin anti-CD105-saporin alone significantly reduced the viability of the CD105-expressing 5-FUR cells, whereas little effect was seen in the CD105-negative non-resistant parental cancer cell lines. Strikingly, using the intracellular drug delivery method photochemical internalization (PCI) by combining light-controlled activation of the TPCS2a with nanomolar levels of CD105-saporin resulted in strong cytotoxic effects in the 5-FUR cell population. CONCLUSION Our findings suggested that autophagy is an important resistance mechanism against the chemotherapeutic drug 5-FU in pancreatic cancer cells, and that inhibition of the autophagy process, either by CQ or lysosomal photodamage, can contribute to increased sensitivity to 5-FU. For the first time, we demonstrate the promise of PCI-based targeting of CD105 in site-specific elimination of 5-FU resistant pancreatic cancer cells in vitro. In conclusion, PCI-based targeting of CD105 may represent a potent anticancer strategy and should be further evaluated in pre-clinical models.
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Affiliation(s)
- Kaja Lund
- Unit for Cell Signaling, Institute of Microbiology, Rikshospitalet, 0372 Oslo, Norway
- Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112, Blindern, 0317 Oslo, Norway
| | - Cathrine Elisabeth Olsen
- Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
| | - Judith Jing Wen Wong
- Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
| | - Petter Angell Olsen
- Unit for Cell Signaling, Institute of Microbiology, Rikshospitalet, 0372 Oslo, Norway
- Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112, Blindern, 0317 Oslo, Norway
| | - Nina Therese Solberg
- Unit for Cell Signaling, Institute of Microbiology, Rikshospitalet, 0372 Oslo, Norway
- Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112, Blindern, 0317 Oslo, Norway
| | - Anders Høgset
- PCI Biotech AS, Ullernchaussèn 64, 0379 Oslo, Norway
| | - Stefan Krauss
- Unit for Cell Signaling, Institute of Microbiology, Rikshospitalet, 0372 Oslo, Norway
- Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112, Blindern, 0317 Oslo, Norway
| | - Pål Kristian Selbo
- Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
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Theodossiou TA, Olsen CE, Jonsson M, Kubin A, Hothersall JS, Berg K. The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy. Redox Biol 2017; 12:191-197. [PMID: 28254657 PMCID: PMC5333531 DOI: 10.1016/j.redox.2017.02.018] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 02/21/2017] [Accepted: 02/23/2017] [Indexed: 12/27/2022] Open
Abstract
The diverse responses of different cancers to treatments such as photodynamic therapy of cancer (PDT) have fueled a growing need for reliable predictive markers for treatment outcome. In the present work we have studied the differential response of two phenotypically and genotypically different breast adenocarcinoma cell lines, MCF7 and MDA-MB-231, to hypericin PDT (HYP-PDT). MDA-MB-231 cells were 70% more sensitive to HYP PDT than MCF7 cells at LD50. MCF7 were found to express a substantially higher level of glutathione peroxidase (GPX4) than MDA-MB-231, while MDA-MB-231 differentially expressed glutathione-S-transferase (GSTP1), mainly used for xenobiotic detoxification. Eighty % reduction of intracellular glutathione (GSH) by buthionine sulfoximine (BSO), largely enhanced the sensitivity of the GSTP1 expressing MDA-MB-231 cells to HYP-PDT, but not in MCF7 cells. Further inhibition of the GSH reduction however by carmustine (BCNU) resulted in an enhanced sensitivity of MCF7 to HYP-PDT. HYP loading studies suggested that HYP can be a substrate of GSTP for GSH conjugation as BSO enhanced the cellular HYP accumulation by 20% in MDA-MB-231 cells, but not in MCF7 cells. Studies in solutions showed that L-cysteine can bind the GSTP substrate CDNB in the absence of GSTP. This means that the GSTP-lacking MCF7 may use L-cysteine for xenobiotic detoxification, especially during GSH synthesis inhibition, which leads to L-cysteine build-up. This was confirmed by the lowered accumulation of HYP in both cell lines in the presence of BSO and the L-cysteine source NAC. NAC reduced the sensitivity of MCF7, but not MDA-MB-231, cells to HYP PDT which is in accordance with the antioxidant effects of L-cysteine and its potential as a GSTP substrate. As a conclusion we have herein shown that the different GSH based cell defense mechanisms can be utilized as predictive markers for the outcome of PDT and as a guide for selecting optimal combination strategies.
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Affiliation(s)
- Theodossis A Theodossiou
- Department of Radiation Biology, Institute for cancer Research, Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway.
| | - Cathrine E Olsen
- Department of Radiation Biology, Institute for cancer Research, Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway
| | - Marte Jonsson
- Department of Radiation Biology, Institute for cancer Research, Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway
| | - Andreas Kubin
- PLANTA Naturstoffe Vertriebs GmbH, A-1120 Wien, Austria
| | - John S Hothersall
- Department of Radiation Biology, Institute for cancer Research, Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway
| | - Kristian Berg
- Department of Radiation Biology, Institute for cancer Research, Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway
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Dąbrowski JM. Reactive Oxygen Species in Photodynamic Therapy: Mechanisms of Their Generation and Potentiation. ADVANCES IN INORGANIC CHEMISTRY 2017. [DOI: 10.1016/bs.adioch.2017.03.002] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Ju E, Dong K, Chen Z, Liu Z, Liu C, Huang Y, Wang Z, Pu F, Ren J, Qu X. Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy. Angew Chem Int Ed Engl 2016. [DOI: 10.1002/ange.201605509] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Enguo Ju
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Kai Dong
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Zhaowei Chen
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Zhen Liu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Chaoqun Liu
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Yanyan Huang
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Zhenzhen Wang
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Fang Pu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Jinsong Ren
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Xiaogang Qu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
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Ju E, Dong K, Chen Z, Liu Z, Liu C, Huang Y, Wang Z, Pu F, Ren J, Qu X. Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy. Angew Chem Int Ed Engl 2016; 55:11467-71. [DOI: 10.1002/anie.201605509] [Citation(s) in RCA: 303] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Indexed: 12/21/2022]
Affiliation(s)
- Enguo Ju
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Kai Dong
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Zhaowei Chen
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Zhen Liu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Chaoqun Liu
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Yanyan Huang
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Zhenzhen Wang
- University of Chinese Academy of Sciences; Beijing 100039 P.R. China
| | - Fang Pu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Jinsong Ren
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
| | - Xiaogang Qu
- Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization; Changchun Institute of Applied Chemistry, Chinese Academy of Science; Changchun, Jilin 130022 P.R. China
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Fan H, Yan G, Zhao Z, Hu X, Zhang W, Liu H, Fu X, Fu T, Zhang XB, Tan W. A Smart Photosensitizer-Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells. Angew Chem Int Ed Engl 2016; 55:5477-82. [PMID: 27010667 DOI: 10.1002/anie.201510748] [Citation(s) in RCA: 423] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 12/28/2015] [Indexed: 12/25/2022]
Abstract
Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.
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Affiliation(s)
- Huanhuan Fan
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Guobei Yan
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Zilong Zhao
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Wenhan Zhang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Hui Liu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Xiaoyi Fu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.,Department of Chemistry and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL, 32611-7200, USA
| | - Ting Fu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China
| | - Xiao-Bing Zhang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
| | - Weihong Tan
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China. .,Department of Chemistry and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL, 32611-7200, USA.
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Fan H, Yan G, Zhao Z, Hu X, Zhang W, Liu H, Fu X, Fu T, Zhang X, Tan W. A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells. Angew Chem Int Ed Engl 2016. [DOI: 10.1002/ange.201510748] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Huanhuan Fan
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Guobei Yan
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Zilong Zhao
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Wenhan Zhang
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Hui Liu
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Xiaoyi Fu
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
- Department of Chemistry and Physiology and Functional Genomics Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute University of Florida Gainesville FL 32611-7200 USA
| | - Ting Fu
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Xiao‐Bing Zhang
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
| | - Weihong Tan
- Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China
- Department of Chemistry and Physiology and Functional Genomics Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute University of Florida Gainesville FL 32611-7200 USA
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Soares HT, Campos JRS, Gomes-da-Silva LC, Schaberle FA, Dabrowski JM, Arnaut LG. Pro-oxidant and Antioxidant Effects in Photodynamic Therapy: Cells Recognise that Not All Exogenous ROS Are Alike. Chembiochem 2016; 17:836-42. [DOI: 10.1002/cbic.201500573] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Indexed: 12/25/2022]
Affiliation(s)
- Helder T. Soares
- Chemistry Department; Universidade de Coimbra; Rua Larga 3004-535 Coimbra Portugal
| | - Joana R. S. Campos
- Chemistry Department; Universidade de Coimbra; Rua Larga 3004-535 Coimbra Portugal
| | | | | | - Janusz M. Dabrowski
- Faculty of Chemistry; Jagiellonian University; Ingardena 3 30-060 Kraków Poland
| | - Luis G. Arnaut
- Chemistry Department; Universidade de Coimbra; Rua Larga 3004-535 Coimbra Portugal
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Giammanco M, Di Majo D, La Guardia M, Aiello S, Crescimannno M, Flandina C, Tumminello FM, Leto G. Vitamin D in cancer chemoprevention. PHARMACEUTICAL BIOLOGY 2015; 53:1399-1434. [PMID: 25856702 DOI: 10.3109/13880209.2014.988274] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
CONTEXT There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. OBJECTIVE The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. METHODS A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. RESULTS AND CONCLUSION Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.
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Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 11:657-70. [DOI: 10.1016/j.nano.2014.12.007] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 11/21/2014] [Accepted: 12/09/2014] [Indexed: 12/15/2022]
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50
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MicroRNAs associated with the efficacy of photodynamic therapy in biliary tract cancer cell lines. Int J Mol Sci 2014; 15:20134-57. [PMID: 25380521 PMCID: PMC4264160 DOI: 10.3390/ijms151120134] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 08/27/2014] [Accepted: 10/27/2014] [Indexed: 12/18/2022] Open
Abstract
Photodynamic therapy (PDT) is a palliative treatment option for unresectable hilar biliary tract cancer (BTC) showing a considerable benefit for survival and quality of life with few side effects. Currently, factors determining the cellular response of BTC cells towards PDT are unknown. Due to their multifaceted nature, microRNAs (miRs) are a promising analyte to investigate the cellular mechanisms following PDT. For two photosensitizers, Photofrin® and Foscan®, the phototoxicity was investigated in eight BTC cell lines. Each cell line (untreated) was profiled for expression of n=754 miRs using TaqMan® Array Human MicroRNA Cards. Statistical analysis and bioinformatic tools were used to identify miRs associated with PDT efficiency and their putative targets, respectively. Twenty miRs correlated significantly with either high or low PDT efficiency. PDT was particularly effective in cells with high levels of clustered miRs 25-93*-106b and (in case of miR-106b) a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression). Insensitivity towards PDT was associated with high miR-200 family expression and (for miR-cluster 200a/b-429) expression of differentiation markers Ck19 and Ck8/18. Predicted and validated downstream targets indicate plausible involvement of miRs 20a*, 25, 93*, 130a, 141, 200a, 200c and 203 in response mechanisms to PDT, suggesting that targeting these miRs could improve susceptibility to PDT in insensitive cell lines. Taken together, the miRNome pattern may provide a novel tool for predicting the efficiency of PDT and-following appropriate functional verification-may subsequently allow for optimization of the PDT protocol.
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