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1
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Zhou W, Liu Y, Nie X, Zhu C, Xiong L, Zhou J, Huang W. Peptide-based inflammation-responsive implant coating sequentially regulates bone regeneration to enhance interfacial osseointegration. Nat Commun 2025; 16:3283. [PMID: 40189598 PMCID: PMC11973180 DOI: 10.1038/s41467-025-58444-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/20/2025] [Indexed: 04/09/2025] Open
Abstract
Aseptic loosening is the primary cause of bone prosthesis failure, commonly attributed to inadequate osseointegration due to coatings misaligned with bone regeneration. Here, we modify the titanium surface with a mussel-inspired peptide to form a 3,4-dihydroxyphenylalanine (DOPA)-rich coating, then graft N3-K15-PVGLIG-K23 (P1) and N3-Y5-PVGLIG-K23 (P2), which are composed of anti-inflammatory (K23), angiogenic (K15), osteogenic (Y5), and inflammation-responsive (PVGLIG) sequences, onto the surface via click chemistry, forming the DOPA-P1@P2 coating. DOPA-P1@P2 promotes bone regeneration through sequential regulation. In the initial stage, the outermost K23 induces M2 macrophage polarization, establishing a pro-regenerative immune microenvironment. Subsequently, K15 and Y5, exposed by the release of K23, enhance angiogenesis and osteogenesis. In the final stage, DOPA-P1@P2 outperforms the TiO₂ control, showing a 161% increase in maximal push-out force, a 207% increase in bone volume fraction, and a 1409% increase in bone-to-implant contact. These findings show that DOPA-P1@P2 efficiently enhances interfacial osseointegration by sequentially regulating bone regeneration, providing viable insights into coating design.
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Affiliation(s)
- Wei Zhou
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Liu
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Xuan Nie
- Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, University of Science and Technology of China, Hefei, China
| | - Chen Zhu
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
| | - Liming Xiong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Jing Zhou
- Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
| | - Wei Huang
- Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
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2
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Xiao T, Chen D, Peng L, Li Z, Pan W, Dong Y, Zhang J, Li M. Fluorescence-guided Surgery for Hepatocellular Carcinoma: From Clinical Practice to Laboratories. J Clin Transl Hepatol 2025; 13:216-232. [PMID: 40078203 PMCID: PMC11894393 DOI: 10.14218/jcth.2024.00375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/06/2024] [Accepted: 12/12/2024] [Indexed: 03/14/2025] Open
Abstract
Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.
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Affiliation(s)
- Tian Xiao
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Didi Chen
- Hubei Key Laboratory of Purification and Application of Plant Anti-Cancer Active Ingredients, Hubei University of Education, Wuhan, Hubei, China
| | - Li Peng
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuoxia Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenming Pan
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuping Dong
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Jinxiang Zhang
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Wang Y, Xu Y, Qu Y, Jin Y, Cao J, Zhan J, Li Z, Chai C, Huang C, Li M. Ferroptosis: A novel cell death modality as a synergistic therapeutic strategy with photodynamic therapy. Photodiagnosis Photodyn Ther 2025; 51:104463. [PMID: 39736368 DOI: 10.1016/j.pdpdt.2024.104463] [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: 09/03/2024] [Revised: 12/24/2024] [Accepted: 12/27/2024] [Indexed: 01/01/2025]
Abstract
Although there has been significant progress in current comprehensive anticancer treatments centered on surgery, postoperative recurrence and tumor metastasis still significantly affect both prognosis and quality of life of the patient. Hence, the development of precisely targeted tumor therapies and exploration of immunotherapy represent additional strategies for tumor treatment. Photodynamic therapy (PDT) is a relatively safe treatment modality that not only induces multiple modes of tumor cell death but also mediates the secondary immunological responses against tumor resistance and metastasis. Ferroptosis, an iron-dependent type of programmed cell death characterized by accumulation of reactive oxygen species and lipid peroxidation products to lethal levels, has emerged as an attractive target trigger for tumor therapies. Recent research has revealed a close association between PDT and ferroptosis, suggesting that combining ferroptosis inducers with PDT could strengthen their synergistic anti-tumor efficiency. Here in this review, we discuss the rationale for combining PDT with ferroptosis inducers and highlight the progress of single-molecule photosensitizers to induce ferroptosis, as well as the applications of photosensitizers combined with other therapeutic drugs for collaborative therapy. Furthermore, given the current research dilemma, we propose potential therapeutic strategies to advance the combined usage of PDT and ferroptosis inducers, providing the basis and guidelines for prospective clinical translation and research directionality with regard to PDT.
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Affiliation(s)
- Yuqing Wang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yiting Xu
- Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research, Wuhan 430022, China
| | - Yong Qu
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yifang Jin
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Juanmei Cao
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Dermatology, First Affiliated Hospital, Shihezi University, Shihezi 832008, China
| | - Jinshan Zhan
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zhuoxia Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chuxing Chai
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Changzheng Huang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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4
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Li X, Wang W, Gao Q, Lai S, Liu Y, Zhou S, Yan Y, Zhang J, Wang H, Wang J, Feng Y, Yang R, Su J, Li B, Liao Y. Intelligent bacteria-targeting ZIF-8 composite for fluorescence imaging-guided photodynamic therapy of drug-resistant superbug infections and burn wound healing. EXPLORATION (BEIJING, CHINA) 2024; 4:20230113. [PMID: 39713199 PMCID: PMC11655311 DOI: 10.1002/exp.20230113] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 02/02/2024] [Indexed: 12/24/2024]
Abstract
Infected burn wounds are characterized by persistent drug-resistant bacterial infection coupled with an inflammatory response, impeding the wound-healing process. In this study, an intelligent nanoparticle system (CCM+TTD@ZIF-8 NPs) was prepared using curcumin (CCM), an aggregation-induced emission luminogens (TTD), and ZIF-8 for infection-induced wound healing. The CCM+TTD@ZIF-8 NPs showed multiple functions, including bacteria targeting, fluorescence imaging and pH response-guided photodynamic therapy (PDT), and anti-inflammatory. The positive charges of ZIF-8 NPs allowed the targeting of drug-resistant bacteria in infected wounds, thereby realizing fluorescence imaging of bacteria by emitting red fluorescence at the infected site upon blue light irradiation. The pH-responsive characteristics of the CCM+TTD@ZIF-8 NPs also enabled controllable CCM release onto the infected wound site, thereby promoting the specific accumulation of ROS at the infected site, with outstanding bactericidal efficacy against drug-resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) strains in vitro/in vivo. Additionally, due to the excellent bactericidal effect and anti-inflammatory properties of CCM+TTD@ZIF-8 NPs combined with blue light irradiation, the regeneration of epidermal tissue, angiogenesis, and collagen deposition was achieved, accelerating the healing process of infected burn wounds. Therefore, this CCM+TTD@ZIF-8 NPs with multifunctional properties provides great potential for infected burn wound healing.
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Affiliation(s)
- Xiaoxue Li
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Wei Wang
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Qiuxia Gao
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
- School of InspectionNingxia Medical UniversityYinchuanNingxiaChina
| | - Shanshan Lai
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Yan Liu
- Institute for Health Innovation and TechnologyNational University of SingaporeSingaporeSingapore
| | - Sitong Zhou
- Department of DermatologyThe First People's Hospital of FoshanFoshanGuangdongChina
| | - Yan Yan
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Jie Zhang
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Huanhuan Wang
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Jiamei Wang
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Yi Feng
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
| | - Ronghua Yang
- Department of Burn and Plastic SurgeryGuangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdongChina
| | - Jianyu Su
- School of Food Science and EngineeringSouth China University of TechnologyGuangzhouGuangdongChina
| | - Bin Li
- School of InspectionNingxia Medical UniversityYinchuanNingxiaChina
| | - Yuhui Liao
- Molecular Diagnosis and Treatment Center for Infectious DiseasesDermatology Hospital of Southern Medical UniversityGuangzhouGuangdongChina
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5
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Lei Y, Ji Z, Xiang W, Duan L. A dual-state emission luminogen for lipid droplet imaging and photodynamic therapy. Bioorg Chem 2024; 153:107856. [PMID: 39362082 DOI: 10.1016/j.bioorg.2024.107856] [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: 08/22/2024] [Revised: 09/21/2024] [Accepted: 09/28/2024] [Indexed: 10/05/2024]
Abstract
Organic luminogens with dual-state emission (DSE) have garnered widespread attention due to their versatility in the forms of both dilute solutions and solids. Despite the growing interest, most research on DSE focuses primarily on molecule design and photophysical investigation, with limited exploration of their practical applications. In this study, we introduce a novel fluorescent molecule, PCT, featuring a distinct D-π(A)-D' electronic structure. PCT exhibited efficient DSE properties, with high quantum yields in both dilute solutions (ΦTHF = 52.3 %) and solid-state (Φsolid = 74.6 %). Taking advantage of PCT's lipophilicity, we demonstrated its potential for targeted lipid droplet (LD) imaging in living cells and its utility in monitoring LD depletion during cellular starvation. To further enhance its applicability in photodynamic therapy (PDT), PCT was encapsulated within the amphiphilic triblock copolymer Pluronic F127, forming PCT@F127 nanoparticles with improved colloidal stability. These nanoparticles efficiently generated singlet oxygen (1O2) under white light irradiation, achieving a 1O2 quantum yield of 57.2 %. In vitro studies on MCF-7 cells revealed significant 1O2 generation and potent phototoxicity, leading to marked cell apoptosis and necrosis. These results underscore PCT's multifunctionality as a DSEgen, with promising applications in both bioimaging and PDT.
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Affiliation(s)
- Yu Lei
- Department of Emergency Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun 130021, China
| | - Zhiyong Ji
- Department of Emergency Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun 130021, China.
| | - Wei Xiang
- Department of Emergency Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun 130021, China
| | - Liming Duan
- Department of Emergency Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun 130021, China
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6
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Qiao Y, Tang X, Qiuju X, Zhang G. Enzyme-loaded manganese-porphyrin metal-organic nanoframeworks for oxygen-evolving photodynamic therapy of hypoxic cells. Heliyon 2024; 10:e33902. [PMID: 39071555 PMCID: PMC11282992 DOI: 10.1016/j.heliyon.2024.e33902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/30/2024] Open
Abstract
Photodynamic therapy (PDT) is attracting great attention for cancer treatments, while its therapeutic efficacy is limited by unsatisfactory photosensitizers and hypoxic tumor microenvironment (TME). To address these problems, we have developed catalase-loaded manganese-porphyrin frameworks (CAT@MnPFs) for catalytically-assisted PDT of cancer cells. CAT@MnPFs were constructed by the assembly of Mn2+ ions and PpIX into MnPFs and the subsequent loading of catalase. Under 650 nm light irradiation, the porphyrin (Protoporphyrin IX) within the structure of CAT@MnPFs can convert oxygen (O2) into singlet oxygen (1O2), showing the photodynamic effect. Importantly, the loaded catalase can decompose hydrogen peroxide (H2O2) into O2 with a huge elevation of O2 level (13.22 mg L-1) in 600 s, thus promoting 1O2 generation via PDT. As a result, CAT@MnPFs combined with 650 nm light can effectively ablate cancer cells due to the catalase-assisted oxygen-evolving PDT, showing a high therapeutic efficacy. Meanwhile, after the incubation with CAT@MnPFs, unobvious damage can be found in normal and red blood cells. Thus, the obtained CAT@MnPFs integrate the advantage of photosensitizers and catalase for oxygen-evolving PDT, which can provide some insight for treating hypoxic cells.
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Affiliation(s)
- Yang Qiao
- Department of Hematology and Oncology, Wenzhou Medical University affiliated Huangyan Hospital, The First People's Hospital of Taizhou, People's Republic of China
| | - Xiaowan Tang
- Department of Hematology and Oncology, Wenzhou Medical University affiliated Huangyan Hospital, The First People's Hospital of Taizhou, People's Republic of China
| | - Xu Qiuju
- The Third Affiliated Hospital of Harbin Medical University, 150 Haping Rd, Harbin, Heilongjiang Province, People's Republic of China
| | - Guangwen Zhang
- Department of Hematology and Oncology, Wenzhou Medical University affiliated Huangyan Hospital, The First People's Hospital of Taizhou, People's Republic of China
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7
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Zhao X, Wu X, Shang R, Chen H, Tan N. A structure-guided strategy to design Golgi apparatus-targeted type-I/II aggregation-induced emission photosensitizers for efficient photodynamic therapy. Acta Biomater 2024; 183:235-251. [PMID: 38801870 DOI: 10.1016/j.actbio.2024.05.034] [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: 11/06/2023] [Revised: 05/09/2024] [Accepted: 05/21/2024] [Indexed: 05/29/2024]
Abstract
The Golgi apparatus (GA) is a vital target for anticancer therapy due to its sensitivity against reactive oxygen species (ROS)-induced oxidative stress that could lead to cell death. In this study, we designed a series of aggregation-induced emission (AIE)-based photosensitizers (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) carrying different ROS with selective GA-targeted ability. The in vitro study showed that TPAPyTZ and TPAPyTC displayed strong AIE characteristics, robust type-I/II ROS production capabilities, specific GA-targeted, high photostability, and high imaging quality. The cell-uptake of TPAPyTZ was found primarily through an energy-dependent caveolae/raft-mediated endocytosis pathway. Remarkably, TPAPyTZ induced GA-oxidative stress, leading to GA fragmentation, downregulation of GM130 expression, and activation of mitochondria caspase-related apoptosis during photodynamic therapy (PDT). In vivo experiments revealed that TPAPyTZ significantly inhibited tumor proliferation under lower-intensity white light irradiation with minimal side effects. Overall, our work presents a promising strategy for designing AIEgens for fluorescence imaging-guided PDT. Additionally, it enriched the collection of GA-targeted leads for the development of cancer theranostics capable of visualizing dynamic changes in the GA during cancer cell apoptosis, which could potentially enable early diagnosis applications in the future. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) are potent phototheranostic agents that can exhibit strong fluorescence emission and enhance ROS production in the aggregate states. In this study, through the precise design of photosensitizers with four different electron-acceptors, we constructed a series of potent AIEgens (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) with strong fluorescence intensity and ROS generation capacity. Among them, TPAPyTZ with an extended π-conjugation displayed the strongest ROS generation ability and anti-tumor activity, resulting in an 88 % reduction in tumor weight. Our studies revealed that the enhanced activity of TPAPyTZ may be due to its unique Golgi apparatus (GA)-targeted ability, which causes GA oxidative stress followed by effective cancer cell apoptosis. This unique GA-targeted feature of TPAPyTZ remains rare in the reported AIEgens, which mainly target organelles such as lysosome, mitochondria, and cell membrane. The successful design of a GA-targeted and potent AIEgen could enrich the collection of GA-targeted luminogens, providing a lead theranostic for the further development of fluorescence imaging-guided PDT, and serving as a tool to explore the potential mechanism and discover new GA-specific drug targets.
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Affiliation(s)
- Xing Zhao
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Xi Wu
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Ranran Shang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Huachao Chen
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
| | - Ninghua Tan
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
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8
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Sun H, Li L, Guo R, Wang Z, Guo Y, Li Z, Song F. Suppressing ACQ of molecular photosensitizers by distorting the conjugated-plane for enhanced tumor photodynamic therapy. Chem Sci 2024; 15:940-952. [PMID: 38239684 PMCID: PMC10793593 DOI: 10.1039/d3sc05041f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 12/11/2023] [Indexed: 01/22/2024] Open
Abstract
Non-AIE-type molecular photosensitizers (PSs) suffer from the aggregation-caused-quenching (ACQ) effect in an aqueous medium due to the strong hydrophobic and π-π interactions of their conjugated planes, which significantly hinders the enhancement of tumor photodynamic therapy (PDT). So far, some ionic PSs have been reported with good water-solubility, though the ACQ effect can still be induced in a biological environment rich in ions, leading to unsatisfactory in vivo delivery and fluorescence imaging performance. Hence, designing molecular PSs with outstanding anti-ACQ properties in water is highly desirable, but it remains a tough challenge for non-AIE-type fluorophores. Herein, we demonstrated a strategy for the design of porphyrin-type molecular PSs with remarkable solubility and anti-ACQ properties in an aqueous medium, which was assisted by quantum chemical simulations. It was found that cationic branched side chains can induce serious plane distortion in diphenyl porphyrin (DPP), which was not observed for tetraphenyl porphyrin (TPP) with the same side chains. Moreover, the hydrophilicity of the chain spacer is also crucial to the plane distortion for attaining the desired anti-ACQ properties. Compared to ACQ porphyrin, anti-ACQ porphyrin displayed type-I ROS generation in hypoxia and much higher tumor accumulation efficacy by blood circulation, leading to highly efficient in vivo PDT for hypoxic tumors. This study demonstrates the power of sidechain chemistry in tuning the configuration and aggregation behaviors of porphyrins in water, offering a new path to boost the performance of PSs to fulfill the increasing clinical demands on cancer theranostics.
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Affiliation(s)
- Han Sun
- Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University Qingdao Shandong 266237 China
| | - Lukun Li
- Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University Qingdao Shandong 266237 China
| | - Ruihua Guo
- Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University Qingdao Shandong 266237 China
| | - Zhe Wang
- Department of Materials Science and Engineering, Hainan University Haikou Hainan 570228 China
| | - Yanhui Guo
- Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University Qingdao Shandong 266237 China
| | - Zhiliang Li
- Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University Qingdao Shandong 266237 China
| | - Fengling Song
- Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University Qingdao Shandong 266237 China
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Shi P, Sun X, Yuan H, Chen K, Bi S, Zhang S. Nanoscale Metal-Organic Frameworks Combined with Metal Nanoparticles and Metal Oxide/Peroxide to Relieve Tumor Hypoxia for Enhanced Photodynamic Therapy. ACS Biomater Sci Eng 2023; 9:5441-5456. [PMID: 37729521 DOI: 10.1021/acsbiomaterials.3c00509] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2023]
Abstract
Photodynamic therapy (PDT) is a clinically approved noninvasive tumor therapy that can selectively kill malignant tumor cells, with promising use in the treatment of various cancers. PDT is typically composed of three important parts: the specific wavelength of light, photosensitizer (PS), and oxygen. With the progressing investigation on PDT treatment, the most recent attention has focused on improving photodynamic efficiency. Tumor hypoxia has always been a critical factor hindering the efficacy of PDT. Nanoscale metal-organic frameworks (nMOF), the fourth generation of PS, present great potential in photodynamic therapy. In particular, nMOF combined with metal nanoparticles and metal oxide/peroxide has demonstrated unique properties for enhanced PDT. The metal and metal oxide nanoparticles can catalyze H2O2 to generate oxygen or automatically produces oxygen, alleviating the hypoxia and improving the photodynamic efficiency. Metal peroxide nanoparticles can spontaneously produce oxygen in water or under acidic conditions. Therefore, this Review summarizes the recent development of nMOF combined with metal nanoparticles (platinum nanoparticles and gold nanoparticles) and metal oxide/peroxide (manganese dioxide, ferric oxide, cerium oxide, calcium peroxide, and magnesium peroxide) for enhanced photodynamic therapy by alleviating tumor hypoxia. Finally, future perspectives of nMOF combined nanomaterials in PDT are put forward.
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Affiliation(s)
- Pengfei Shi
- College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong 266071, China
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, Shandong, People's Republic of China
| | - Xinran Sun
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, Shandong, People's Republic of China
| | - Haoming Yuan
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, Shandong, People's Republic of China
| | - Kaixiu Chen
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, Shandong, People's Republic of China
| | - Sai Bi
- College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong 266071, China
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, Shandong, People's Republic of China
| | - Shusheng Zhang
- College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong 266071, China
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, Shandong, People's Republic of China
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10
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Wang DP, Zheng J, Jiang FY, Wu LF, Wang MY, Wang YL, Qin CY, Ning JY, Cao JM, Zhou X. Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy. Acta Biomater 2023; 168:551-564. [PMID: 37414113 DOI: 10.1016/j.actbio.2023.06.048] [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: 12/28/2022] [Revised: 06/25/2023] [Accepted: 06/29/2023] [Indexed: 07/08/2023]
Abstract
In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor‑ and mitochondria‑targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.
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Affiliation(s)
- De-Ping Wang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Jian Zheng
- Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan 030001, China
| | - Fang-Ying Jiang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Li-Fei Wu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Mei-Yue Wang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Yu-Lan Wang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Chuan-Yue Qin
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Jun-Ya Ning
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
| | - Xin Zhou
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; Department of Medical Imaging, Shanxi Medical University, Taiyuan 030001, China.
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11
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Yu H, Wang Q, Zhang X, Tiemuer A, Wang J, Zhang Y, Sun X, Liu Y. Hot-band absorption assisted single-photon frequency upconversion luminescent nanophotosensitizer for 808 nm light triggered photodynamic immunotherapy of cancer. Biomater Sci 2023; 11:2167-2176. [PMID: 36734805 DOI: 10.1039/d2bm01700h] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Frequency upconversion luminescence (FUCL) based on hot-band absorption has attracted considerable attention in bioimaging and phototherapy fields for deep-seated cancer treatment. Photoimmunotherapy, a promising therapeutic approach induced by photodynamic therapy (PDT), can selectively kill cancer cells, reverse the immunosuppressive system, boost host immune response, and elicit durable antitumor immunity. To date, few near-infrared organic photosensitizers for photodynamic immunotherapy have been reported based on hot-band absorption. Herein, we report an upconversion luminescent phthalocyanine photosensitizer PdPc(OBu)8 with anti-Stokes emission at 748 nm and highly efficient singlet oxygen generation with hot-band absorption at 808 nm. Taking advantage of nanoliposomes, FUCL phthalocyanine nano-photosensitizers (PdPc NPs) were obtained to reduce the aggregation-caused quenching and improve water solubility and biocompatibility. PdPc NPs could be effectively accumulated in tumor tissues through intravenous administration, causing FUCL-induced PDT under 808 nm irradiation. Considering its finite immune responses and tumor ablation after PDT, a combination of PdPc NP-based PDT with checkpoint inhibitors (anti-PD-L1) for near-infrared photoimmunotherapy has been used to potentiate the antitumor efficacy that could simultaneously ablate primary tumors and inhibit the progression of distant tumors. This study can promote the development of upconversion-based PDT combined with immunotherapy for tumor precision therapy.
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Affiliation(s)
- Hui Yu
- School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
| | - Qing Wang
- School of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 211198, China.
| | - Xinmiao Zhang
- School of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 211198, China.
| | - Aliya Tiemuer
- School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
| | - Jing Wang
- School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
| | - Yuanyuan Zhang
- School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
| | - Xiaolian Sun
- School of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 211198, China.
| | - Yi Liu
- School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
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12
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Ma X, Kuang L, Yin Y, Tang L, Zhang Y, Fan Q, Wang B, Dong Z, Wang W, Yin T, Wang Y. Tumor-Antigen Activated Dendritic Cell Membrane-Coated Biomimetic Nanoparticles with Orchestrating Immune Responses Promote Therapeutic Efficacy against Glioma. ACS NANO 2023; 17:2341-2355. [PMID: 36688797 DOI: 10.1021/acsnano.2c09033] [Citation(s) in RCA: 73] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Immunotherapy has had a profound positive effect on certain types of cancer but has not improved the outcomes of glioma because of the blood-brain barrier (BBB) and immunosuppressive tumor microenvironment. In this study, we developed an activated mature dendritic cell membrane (aDCM)-coated nanoplatform, rapamycin (RAPA)-loaded poly(lactic-co-glycolic acid) (PLGA), named aDCM@PLGA/RAPA, which is a simple, efficient, and individualized strategy to cross the BBB and improve the immune microenvironment precisely. In vitro cells uptake and the transwell BBB model revealed that the aDCM@PLGA/RAPA can enhance homotypic-targeting and BBB-crossing efficiently. According to the in vitro and in vivo immune response efficacy of aDCM@PLGA/RAPA, the immature dendritic cells (DCs) could be stimulated into the matured status, which leads to further activation of immune cells, such as tumor-infiltrating T cells and natural killer cells, and can induce the subsequent immune responses through direct and indirect way. The aDCM@PLGA/RAPA treatment can not only inhibit glioma growth significantly but also has favorable potential ability to induce glial differentiation in the orthotopic glioma. Moreover, the aDCM@PLGA could induce a robust CD8+ effector and therefore suppress orthotopic glioma growth in a prophylactic setup, which indicates certain tumor immunity. Overall, our work provides an effective antiglioma drug delivery system which has great potential for tumor combination immunotherapy.
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Affiliation(s)
- Xiaoyue Ma
- School of Medicine, Chongqing University, Chongqing 400044, China
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Lei Kuang
- School of Medicine, Chongqing University, Chongqing 400044, China
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Ying Yin
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Lin Tang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Yu Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Qin Fan
- School of Medicine, Chongqing University, Chongqing 400044, China
| | - Bingyi Wang
- School of Medicine, Chongqing University, Chongqing 400044, China
| | - Zhufeng Dong
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Wei Wang
- Department of Biology and Biotechnology, Sapienza University of Rome, Sapienza University of Rome, Rome 00185, Italy
| | - Tieying Yin
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Yazhou Wang
- School of Medicine, Chongqing University, Chongqing 400044, China
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
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13
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Jiang W, Cheng C, Qiu X, Chen L, Guo X, Luo Y, Wang J, Wang J, Xie Z, Li P, Wang Z, Ran H, Zhou Z, Ren J. Peptide Supramolecular Assembly-Instructed In Situ Self-Aggregation for Stratified Targeting Sonodynamic Therapy Enhancement of AIE Luminogens. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2204989. [PMID: 36494092 PMCID: PMC9896067 DOI: 10.1002/advs.202204989] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/18/2022] [Indexed: 06/01/2023]
Abstract
The emergence of aggregation-induced emission luminogens (AIEgens) has attracted substantial scientific attention. However, their antitumor efficacy in photodynamic therapy (PDT) is significantly restricted by the poor water solubility and limited treatment depth. Therefore, a novel AIEgens-involved therapeutic platform with good permeability and bioavailability is urgently required. Herein, supramolecular chemistry is combined with the AIEgen bis-pyrene (BP) to construct a peptide-AIEgen hybrid nanosystem (PAHN). After intravenous injection, the versatile nanoplatform not only improved the hydrophilicity of BP but also achieved stratified targeting from tumor to mitochondrial and induced mitochondrial dysfunction, thus activating caspase-3 upregulation. Then, sonodynamic therapy (SDT), an alternative modality with high tissue penetrability, is performed to evoke reactive oxygen species (ROS) generation for BP. More importantly, since the hydrophilic shell is separated from the nanosystem by the specific cleavage of caspase-3, the resulting decrease in hydrophilicity induced tight self-aggregation of PAHN residues in situ, further allowing more absorbed energy to be used for ROS generation under ultrasound irradiation and enhancing SDT efficacy. Moreover, severe oxidative stress resulting from ROS imbalance in the mitochondria initiates the immunogenic cell death process, thus evoking antitumor immunogenicity. This PAHN provides prospective ideas into AIE-involved antitumor therapy and design of peptide-AIEgens hybrids.
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Affiliation(s)
- Weixi Jiang
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Chen Cheng
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
- Department of UltrasoundBishan Hospital of ChongqingBishan Hospital of Chongqing Medical UniversityNo. 9 Shuangxing Avenue, Biquan Street, Bishan DistrictChongqing402760P. R. China
| | - Xiaoling Qiu
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
- Department of Intensive Care Unitthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Li Chen
- Department of Intensive Care Unitthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Xun Guo
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Yuanli Luo
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Jingxue Wang
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Junrui Wang
- Department of Radiologythe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Zhuoyan Xie
- Department of UltrasoundChongqing General HospitalNO. 118 Xingguang Avenue, Liangjiang New AreaChongqing401147P. R. China
| | - Pan Li
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Zhigang Wang
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Haitao Ran
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
| | - Zhiyi Zhou
- Department of General practiceChongqing General HospitalNO. 118 Xingguang Avenue, Liangjiang New AreaChongqing401147P. R. China
| | - Jianli Ren
- Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imagingthe Second Affiliated Hospital of Chongqing Medical UniversityNo.74 Linjiang Rd, Yuzhong DistrictChongqing400010P. R. China
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14
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Gao Y, Su Z, Wang C, Xu J, Hu S, Zhang C, Sun P, Zhou X, Wang W, Zou T, Yang B, Cheng X, Yi X, Zheng Q. Light-triggered polymeric prodrug and nano-assembly for chemo-photodynamic therapy and potentiate immune checkpoint blockade immunotherapy for hepatocellular carcinoma. MATERIALS & DESIGN 2023; 225:111457. [DOI: 10.1016/j.matdes.2022.111457] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
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15
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Siva S, Jin JO, Choi I, Kim M. Nanoliposome based biosensors for probing mycotoxins and their applications for food: A review. Biosens Bioelectron 2023; 219:114845. [PMID: 36327568 DOI: 10.1016/j.bios.2022.114845] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 09/28/2022] [Accepted: 10/19/2022] [Indexed: 11/19/2022]
Abstract
Mycotoxins are the most common feed and food contaminants affecting animals and humans, respectively; continuous exposure causes tremendous health problems such as kidney disorders, infertility, immune suppression, liver inflammation, and cancer. Consequently, their control and quantification in food materials is crucial. Biosensors are potential tools for the rapid detection and quantification of mycotoxins with high sensitivity and selectivity. Nanoliposomes (NLs) are vesicular carriers formed by self-assembling phospholipids that surround the aqueous cores. Utilizing their biocompatibility, biodegradability, and high carrying capacity, researchers have employed NLs in biosensors for monitoring various targets in biological and food samples. The NLs are used for surface modification, signal marker delivery, and detection of toxins, bacteria, pesticides, and diseases. Here, we review marker-entrapped NLs used in the development of NL-based biosensors for mycotoxins. These biosensors are sensitive, selective, portable, and cost-effective analytical tools, and the resulting signal can be produced and/or amplified with or without destroying the NLs. In addition, this review emphasizes the benefits of the immunoliposome method in comparison with traditional detection approaches. We expect this review to serve as a valuable reference for researchers in this rapidly growing field. The insights provided may facilitate the rational design of next-generation NL-based biosensors.
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Affiliation(s)
- Subramanian Siva
- Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea; Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea.
| | - Jun-O Jin
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea; Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea.
| | - Inho Choi
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea; Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea.
| | - Myunghee Kim
- Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea; Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea.
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16
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Pramanik SK, Sreedharan S, Tiwari R, Dutta S, Kandoth N, Barman S, Aderinto SO, Chattopadhyay S, Das A, Thomas JA. Nanoparticles for super-resolution microscopy: intracellular delivery and molecular targeting. Chem Soc Rev 2022; 51:9882-9916. [PMID: 36420611 DOI: 10.1039/d1cs00605c] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Following an overview of the approaches and techniques used to acheive super-resolution microscopy, this review presents the advantages supplied by nanoparticle based probes for these applications. The various clases of nanoparticles that have been developed toward these goals are then critically described and these discussions are illustrated with a variety of examples from the recent literature.
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Affiliation(s)
- Sumit Kumar Pramanik
- CSIR - Central Salt and Marine Chemicals Research Institute, Gijubhai Badheka Marg, Bhavnagar, Gujarat 364002, India.
| | - Sreejesh Sreedharan
- Human Science Research Centre, University of Derby, Kedleston road, DE22 1GB, UK
| | - Rajeshwari Tiwari
- CSIR - Central Salt and Marine Chemicals Research Institute, Gijubhai Badheka Marg, Bhavnagar, Gujarat 364002, India.
| | - Sourav Dutta
- Department of Chemical Sciences and Centre for Advanced Functional Materials, Indian Institute of Science Education and Research, Kolkata, West Bengal, India.
| | - Noufal Kandoth
- Department of Chemical Sciences and Centre for Advanced Functional Materials, Indian Institute of Science Education and Research, Kolkata, West Bengal, India.
| | - Surajit Barman
- Department of Chemical Sciences and Centre for Advanced Functional Materials, Indian Institute of Science Education and Research, Kolkata, West Bengal, India.
| | - Stephen O Aderinto
- Department of Chemistry, University of Sheffield, Western Bank, Sheffield, S3 7HF, UK.
| | - Samit Chattopadhyay
- Department of Biological Sciences, BITS-Pilani, K K Birla Goa Campus, NH 17B, Zuarinagar, Goa 403726, India.
| | - Amitava Das
- Department of Chemical Sciences and Centre for Advanced Functional Materials, Indian Institute of Science Education and Research, Kolkata, West Bengal, India.
| | - Jim A Thomas
- Department of Chemistry, University of Sheffield, Western Bank, Sheffield, S3 7HF, UK.
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17
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Sun J, Bai Y, Yu EY, Ding G, Zhang H, Duan M, Huang P, Zhang M, Jin H, Kwok RT, Li Y, Shan GG, Tang BZ, Wang H. Self-cleaning wearable masks for respiratory infectious pathogen inactivation by type I and type II AIE photosensitizer. Biomaterials 2022; 291:121898. [PMID: 36379162 PMCID: PMC9647237 DOI: 10.1016/j.biomaterials.2022.121898] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 10/23/2022] [Accepted: 10/30/2022] [Indexed: 11/11/2022]
Abstract
Although face masks as personal protective equipment (PPE) are recommended to control respiratory diseases with the on-going COVID-19 pandemic, improper handling and disinfection increase the risk of cross-contamination and compromise the effectiveness of PPE. Here, we prepared a self-cleaning mask based on a highly efficient aggregation-induced emission photosensitizer (TTCP-PF6) that can destroy pathogens by generating Type I and Type II reactive oxygen species (ROS). The respiratory pathogens, including influenza A virus H1N1 strain and Streptococcus pneumoniae (S. pneumoniae) can be inactivated within 10 min of ultra-low power (20 W/m2) white light or simulated sunlight irradiation. This TTCP-PF6-based self-cleaning strategy can also be used against other airborne pathogens, providing a strategy for dealing with different microbes.
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Affiliation(s)
- Jingxuan Sun
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yujie Bai
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Eric Y Yu
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, China
| | - Guanyu Ding
- Institute of Functional Material Chemistry and National & Local United Engineering Lab for Power Battery, Faculty of Chemistry, Northeast Normal University, Changchun, 130024, China
| | - Haili Zhang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Ming Duan
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Pei Huang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Mengyao Zhang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Hongli Jin
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Ryan Tk Kwok
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, China
| | - Yuanyuan Li
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
| | - Guo-Gang Shan
- Institute of Functional Material Chemistry and National & Local United Engineering Lab for Power Battery, Faculty of Chemistry, Northeast Normal University, Changchun, 130024, China.
| | - Ben Zhong Tang
- School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, China.
| | - Hualei Wang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
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18
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Shi Y, Zhu D, Wang D, Liu B, Du X, Wei G, Zhou X. Recent advances of smart AIEgens for photoacoustic imaging and phototherapy. Coord Chem Rev 2022. [DOI: 10.1016/j.ccr.2022.214725] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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19
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Meng Z, Xue H, Wang T, Chen B, Dong X, Yang L, Dai J, Lou X, Xia F. Aggregation-induced emission photosensitizer-based photodynamic therapy in cancer: from chemical to clinical. J Nanobiotechnology 2022; 20:344. [PMID: 35883086 PMCID: PMC9327335 DOI: 10.1186/s12951-022-01553-z] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/08/2022] [Indexed: 12/24/2022] Open
Abstract
Cancer remains a serious threat to human health owing to the lack of effective treatments. Photodynamic therapy (PDT) has emerged as a promising non-invasive cancer treatment that consists of three main elements: photosensitizers (PSs), light and oxygen. However, some traditional PSs are prone to aggregation-caused quenching (ACQ), leading to reduced reactive oxygen species (ROS) generation capacity. Aggregation-induced emission (AIE)-PSs, due to their distorted structure, suppress the strong molecular interactions, making them more photosensitive in the aggregated state instead. Activated by light, they can efficiently produce ROS and induce cell death. PS is one of the core factors of efficient PDT, so proceeding from the design and preparation of AIE-PSs, including how to manipulate the electron donor (D) and receptor (A) in the PSs configuration, introduce heavy atoms or metal complexes, design of Type I AIE-PSs, polymerization-enhanced photosensitization and nano-engineering approaches. Then, the preclinical experiments of AIE-PSs in treating different types of tumors, such as ovarian cancer, cervical cancer, lung cancer, breast cancer, and its great potential clinical applications are discussed. In addition, some perspectives on the further development of AIE-PSs are presented. This review hopes to stimulate the interest of researchers in different fields such as chemistry, materials science, biology, and medicine, and promote the clinical translation of AIE-PSs.
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Affiliation(s)
- Zijuan Meng
- State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China
| | - Huiying Xue
- State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China
| | - Tingting Wang
- State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China
| | - Biao Chen
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, China
| | - Xiyuan Dong
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, China
| | - Lili Yang
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, China.
| | - Jun Dai
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, China.
| | - Xiaoding Lou
- State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China
| | - Fan Xia
- State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China
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20
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Lou XY, Zhang G, Song N, Yang YW. Supramolecular materials based on AIEgens for photo-assisted therapy. Biomaterials 2022; 286:121595. [DOI: 10.1016/j.biomaterials.2022.121595] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/13/2022] [Accepted: 05/17/2022] [Indexed: 12/19/2022]
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21
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Shi X, Tan L, Zhong Y, Shen T, Wang Y, Qiu Z, Zheng Z, Zhu X, Gu Y, Jiang X, Yang J. Synthesis, Characterization and Bioactivity of Three Tetrazole Carboxylate Based Co(II) Complexes. Eur J Inorg Chem 2022. [DOI: 10.1002/ejic.202200097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Xin‐Ya Shi
- Department of Oncology Changshu No.2 People's Hospital Changshu 215500 P.R.China
| | - Li‐Tao Tan
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Yu‐Jie Zhong
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Ting‐Xiao Shen
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Yan‐Hong Wang
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Zi‐Han Qiu
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Zu‐Hui Zheng
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Xiao‐Ge Zhu
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
| | - Yu‐Lan Gu
- Department of Oncology Changshu No.2 People's Hospital Changshu 215500 P.R.China
| | - Xin Jiang
- School of Pharmacy Guilin Medical University Guilin 541004 Guangxi P.R. China
| | - Jie Yang
- Jiangsu Laboratory of Advanced Functional Materials College of Material Engineering Changshu Institute of Technology Changshu 215500 P.R.China
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22
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Shi XY, Shen TX, Zhang AL, Tan LT, Shen WC, Zhong HJ, Zhang SL, Gu YL, Shen L. Rational Design of a Gd(III)–Cu(II) Nanobooster for Chemodynamic Therapy Against Cancer Cells. Front Chem 2022; 10:856495. [PMID: 35464207 PMCID: PMC9021535 DOI: 10.3389/fchem.2022.856495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
Copper (II) containing coordination complexes have attracted much attention for chemodynamic therapy (CDT) against cancer cells. In this study, the bimetallic nanobooster [Gd2Cu(L)2(H2O)10]·6H2O was prepared by a solvothermal method based on tetrazole carboxylic acid ligand H4L [H4L = 3,3-di (1H-tetrazol-5-yl) pentanedioic acid]. It showed considerable cytotoxicity toward three kinds of human cancer cells (HeLa, HepG2, and HT29). The MTT assay showed that the IC50 (half-maximal inhibitory concentration) of the complex NPs on HeLa cells (4.9 μg/ml) is superior to that of HepG2 (11.1 μg/ml) and HT29 (5.5 μg/ml). This result showed that [Gd2Cu(L)2(H2O)10]·6H2O NPs can inhibit cell proliferation in vitro and may be potential candidates for chemodynamic therapy. In addition, the cytotoxicity was also confirmed by the trypan blue staining experiment. The results promise the great potential of Gd(III)–Cu(II) for CDT against cancer cells.
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Affiliation(s)
- Xin-Ya Shi
- Department of Oncology, Changshu No.2 People’s Hospital, Changshu, China
| | - Ting-Xiao Shen
- Jiangsu Laboratory of Advanced Functional Materials, College of Material Engineering, Changshu Institute of Technology, Changshu, China
| | - Ao-Lin Zhang
- Jiangsu Laboratory of Advanced Functional Materials, College of Material Engineering, Changshu Institute of Technology, Changshu, China
| | - Li-Tao Tan
- Jiangsu Laboratory of Advanced Functional Materials, College of Material Engineering, Changshu Institute of Technology, Changshu, China
| | - Wen-Chang Shen
- Jiangsu Laboratory of Advanced Functional Materials, College of Material Engineering, Changshu Institute of Technology, Changshu, China
| | - Hai-Jiang Zhong
- Jiangsu Laboratory of Advanced Functional Materials, College of Material Engineering, Changshu Institute of Technology, Changshu, China
| | - Shun-Lin Zhang
- State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing, China
- *Correspondence: Shun-Lin Zhang, ; Yu-Lan Gu, ; Lei Shen,
| | - Yu-Lan Gu
- Department of Oncology, Changshu No.2 People’s Hospital, Changshu, China
- *Correspondence: Shun-Lin Zhang, ; Yu-Lan Gu, ; Lei Shen,
| | - Lei Shen
- Jiangsu Laboratory of Advanced Functional Materials, College of Material Engineering, Changshu Institute of Technology, Changshu, China
- *Correspondence: Shun-Lin Zhang, ; Yu-Lan Gu, ; Lei Shen,
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23
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Zhang H, Feng Y, Xie X, Song T, Yang G, Su Q, Li T, Li S, Wu C, You F, Liu Y, Yang H. Engineered Mesenchymal Stem Cells as a Biotherapy Platform for Targeted Photodynamic Immunotherapy of Breast Cancer. Adv Healthc Mater 2022; 11:e2101375. [PMID: 34981675 DOI: 10.1002/adhm.202101375] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 12/12/2021] [Indexed: 01/10/2023]
Abstract
Interleukin-12 (IL12) is a pleiotropic cytokine with promising prospects for cancer immunotherapy. Though IL12 gene-based therapy can overcome the fatal hurdle of severe systemic toxicity, targeted delivery and tumor-located expression of IL12 gene remain the challenging issues yet to be solved. Photo-immunotherapy emerging as a novel and precise therapeutic strategy, which elaborately combines immune-activating agents with light-triggered photosensitizers for potentiated anticancer efficacy. Herein, an engineered stem cell-based biotherapy platform (MB/IL12-MSCs) incorporating immune gene plasmid IL12 (pIL12) and photosensitizer methylene blue (MB) is developed to realize tumor-homing delivery of therapeutic agents and photo-immunotherapy efficacy enhancement. The biotherapy platform retained tumor-tropic migration and penetration functions, which improved the intratumoral distribution of therapeutic agents, thereby promoting photodynamic effects and reinforcing immune responses. Importantly, MB/IL12-MSCs restricted the expression and distribution of IL12 at tumor site, which minimized potential toxicity while eliciting sufficient anticancer immunity. In noteworthy, activation of immunity induced by MB/IL12-MSCs established long-term systemic immunologic memory to prevent tumor relapse. The MB/IL12-MSCs outperform their monotherapy counterparts in breast tumor models, and the growth of tumor significantly arrested as well as re-challenging abscopal tumor growth slowdown. Collectively, this work reveals that MSCs-based strategy may advance more efficient, durable, and safer cancer photo-immunotherapy.
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Affiliation(s)
- Hanxi Zhang
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Yi Feng
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Xiaoxue Xie
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Ting Song
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Geng Yang
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Qingqing Su
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Tingting Li
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Shun Li
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Chunhui Wu
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
| | - Fengming You
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese Medicine No. 39 Shi‐er‐qiao Road Chengdu Sichuan 610072 P. R. China
| | - Yiyao Liu
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese Medicine No. 39 Shi‐er‐qiao Road Chengdu Sichuan 610072 P. R. China
| | - Hong Yang
- Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu Sichuan 610054 P. R. China
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24
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Wen M, Yu N, Wu S, Huang M, Qiu P, Ren Q, Zhu M, Chen Z. On-demand assembly of polymeric nanoparticles for longer-blood-circulation and disassembly in tumor for boosting sonodynamic therapy. Bioact Mater 2022; 18:242-253. [PMID: 35387175 PMCID: PMC8961299 DOI: 10.1016/j.bioactmat.2022.03.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/18/2022] [Accepted: 03/06/2022] [Indexed: 12/14/2022] Open
Abstract
Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ∼80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (∼0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H2O2 into O2 to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.
On-demand assembly from molecules to nanoparticles for longer-blood-circulation. On-demand disassembly in presence of hyaluronidase (in tumor) for boosting sonodynamic effects. Efficient damage on cancer cells in-vitro and Significant inhibition of the tumor growth due to the enhanced SDT.
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25
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Zhang Z, Kang M, Tan H, Song N, Li M, Xiao P, Yan D, Zhang L, Wang D, Tang BZ. The fast-growing field of photo-driven theranostics based on aggregation-induced emission. Chem Soc Rev 2022; 51:1983-2030. [PMID: 35226010 DOI: 10.1039/d1cs01138c] [Citation(s) in RCA: 171] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Photo-driven theranostics, also known as phototheranostics, relying on the diverse excited-state energy conversions of theranostic agents upon photoexcitation represents a significant branch of theranostics, which ingeniously integrate diagnostic imaging and therapeutic interventions into a single formulation. The combined merits of photoexcitation and theranostics endow photo-driven theranostics with numerous superior features. The applications of aggregation-induced emission luminogens (AIEgens), a particular category of fluorophores, in the field of photo-driven theranostics have been intensively studied by virtue of their versatile advantageous merits of favorable biocompatibility, tuneable photophysical properties, unique aggregation-enhanced theranostic (AET) features, ideal AET-favored on-site activation ability and ready construction of one-for-all multimodal theranostics. This review summarised the significant achievements of photo-driven theranostics based on AIEgens, which were detailedly elaborated and classified by their diverse theranostic modalities into three groups: fluorescence imaging-guided photodynamic therapy, photoacoustic imaging-guided photothermal therapy, and multi-modality theranostics. Particularly, the tremendous advantages and individual design strategies of AIEgens in pursuit of high-performance photosensitizing output, high photothermal conversion and multimodal function capability by adjusting the excited-state energy dissipation pathways are emphasized in each section. In addition to highlighting AIEgens as promising templates for modulating energy dissipation in the application of photo-driven theranostics, current challenges and opportunities in this field are also discussed.
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Affiliation(s)
- Zhijun Zhang
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Miaomiao Kang
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Hui Tan
- Pneumology Department, Shenzhen Children's Hospital, Shenzhen 518026, China
| | - Nan Song
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Meng Li
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Peihong Xiao
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Dingyuan Yan
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Liping Zhang
- Pneumology Department, Shenzhen Children's Hospital, Shenzhen 518026, China
| | - Dong Wang
- Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen 518060, China.
| | - Ben Zhong Tang
- Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Boulevard, Longgang District, Shenzhen City, Guangdong 518172, China.
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26
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Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting. Pharmaceutics 2022; 14:pharmaceutics14020459. [PMID: 35214196 PMCID: PMC8877525 DOI: 10.3390/pharmaceutics14020459] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/07/2022] [Accepted: 01/17/2022] [Indexed: 12/16/2022] Open
Abstract
Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness.
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27
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An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment. Int J Mol Sci 2022; 23:ijms23042286. [PMID: 35216400 PMCID: PMC8874418 DOI: 10.3390/ijms23042286] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/17/2022] [Accepted: 02/17/2022] [Indexed: 02/01/2023] Open
Abstract
Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells. The AuNP-mTHPC complex is biocompatible, soluble, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650-nm laser, which decreased mitochondrial membrane potential (∆ψm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Our study aimed at applying the AuNP-mTHPC approach as a potential treatment of cancer in the biomedical field.
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28
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Xia Q, Zhang Y, Li Y, Li Y, Li Y, Feng Z, Fan X, Qian J, Lin H. A historical review of aggregation‐induced emission from 2001 to 2020: A bibliometric analysis. AGGREGATE 2022; 3. [DOI: 10.1002/agt2.152] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2023]
Abstract
AbstractAggregation‐induced emission (AIE) is a photophysical phenomenon that a certain group of luminescent materials that become highly luminous when aggregated in a bad solvent or solid state. This year is the 20th anniversary since the AIE concept firstly proposed in 2001. Many advanced applications were gradually being explored, covering optics, electronics, energy, and bioscience and so on. At present, bibliometrics can enlighten the researchers with comprehensive sights of the achievements and trends of a specific field, which is critical for academic investigations. Herein, we presented a general bibliometric overview of AIE covering 20 years of evolution. With the assistance of Web of Science Core Collection database and several bibliometric software tools, the annual publication and citation, most influential countries/regions, most contributing authors, journals and institutions, second near‐infrared (NIR‐II) related hotspots, as well as the forecast of frontiers were demonstrated and systematically analyzed. This study summarizes the current research status in AIE research field and provides a reference for future research directions.
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Affiliation(s)
- Qiming Xia
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
| | - Yiyin Zhang
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
| | - Yiling Li
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
| | - Yirun Li
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
| | - Yixuan Li
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
| | - Zhe Feng
- State Key Laboratory of Modern Optical Instrumentations Centre for Optical and Electromagnetic Research College of Optical Science and Engineering International Research Center for Advanced Photonics Zhejiang University Hangzhou P. R. China
| | - Xiaoxiao Fan
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
- State Key Laboratory of Modern Optical Instrumentations Centre for Optical and Electromagnetic Research College of Optical Science and Engineering International Research Center for Advanced Photonics Zhejiang University Hangzhou P. R. China
| | - Jun Qian
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
- State Key Laboratory of Modern Optical Instrumentations Centre for Optical and Electromagnetic Research College of Optical Science and Engineering International Research Center for Advanced Photonics Zhejiang University Hangzhou P. R. China
| | - Hui Lin
- Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Zhejiang Province Hangzhou P. R. China
- College of Biomedical Engineering and Instrument Science Zhejiang University Hangzhou P. R. China
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29
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Yang J, Yu X, Song J, Song Q, Hall SCL, Yu G, Perrier S. Aggregation‐Induced Emission Featured Supramolecular Tubisomes for Imaging‐Guided Drug Delivery. Angew Chem Int Ed Engl 2022. [DOI: 10.1002/ange.202115208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Jie Yang
- Department of Chemistry University of Warwick Coventry CV4 7AL UK
- College of Science Nanjing Forestry University Nanjing 210037 P. R. China
| | - Xinyang Yu
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology Department of Chemistry Tsinghua University Beijing 100084 P. R. China
| | - Ji‐Inn Song
- Department of Chemistry University of Warwick Coventry CV4 7AL UK
| | - Qiao Song
- Department of Chemistry University of Warwick Coventry CV4 7AL UK
| | | | - Guocan Yu
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology Department of Chemistry Tsinghua University Beijing 100084 P. R. China
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30
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Abstract
Applications of AIEgens in biosensing, disease diagnosis, and drug release.
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Affiliation(s)
- Guangfu Feng
- School of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, P.R. China
| | - Sijie Liao
- School of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, P.R. China
| | - Yufeng Liu
- School of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, P.R. China
| | - Huaizu Zhang
- School of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, P.R. China
| | - Xingyu Luo
- School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, P.R. China
| | - Xiangming Zhou
- School of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, P.R. China
| | - Jun Fang
- School of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, P.R. China
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31
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Kong C, Xu B, Qiu G, Wei M, Zhang M, Bao S, Tang J, Li L, Liu J. Multifunctional Nanoparticles-Mediated PTT/PDT Synergistic Immune Activation and Antitumor Activity Combined with Anti-PD-L1 Immunotherapy for Breast Cancer Treatment. Int J Nanomedicine 2022; 17:5391-5411. [PMID: 36419717 PMCID: PMC9677922 DOI: 10.2147/ijn.s373282] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 11/08/2022] [Indexed: 11/18/2022] Open
Abstract
Introduction Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues. Methods In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional ICG@SANPs-cRGD nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer. Results The experimental results show that ICG@SANPs-cRGD nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on ICG@SANPs-cRGD can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of ICG@SANPs-cRGD. PTT/PDT combined with Anti-PD-L1 immunotherapy based on ICG@SANPs-cRGD mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body's immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor. Discussion This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on ICG@SANPs-cRGD nanomaterials for breast cancer treatment and demonstrates the potential of ICG@SANPs-cRGD as a multifunctional therapeutic platform for future cancer therapy.
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Affiliation(s)
- Cunqing Kong
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Banghao Xu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Guanhua Qiu
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Meng Wei
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Mengqi Zhang
- Department of Interventional Therapy Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Shengxian Bao
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Jiali Tang
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - JunJie Liu
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
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32
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Pandey NK, Xiong W, Wang L, Chen W, Bui B, Yang J, Amador E, Chen M, Xing C, Athavale AA, Hao Y, Feizi W, Lumata L. Aggregation-induced emission luminogens for highly effective microwave dynamic therapy. Bioact Mater 2022; 7:112-125. [PMID: 34466721 PMCID: PMC8379457 DOI: 10.1016/j.bioactmat.2021.05.031] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/05/2021] [Accepted: 05/20/2021] [Indexed: 02/08/2023] Open
Abstract
Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light. Herein, for the first time, we report AIEgen-mediated microwave dynamic therapy (MWDT) for cancer treatment. We found that two AIEgens (TPEPy-I and TPEPy-PF6) served as a new type of microwave (MW) sensitizers to produce ROS, including singlet oxygen (1O2), resulting in efficient destructions of cancer cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22 μM, respectively. Overall, the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT, but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome, thus reducing the occurrence of side-effects of MW radiation.
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Affiliation(s)
- Nil Kanatha Pandey
- Department of Physics, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Wei Xiong
- Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Lingyun Wang
- Department of Physics, The University of Texas at Arlington, Arlington, TX 76019, USA
- Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Wei Chen
- Department of Physics, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Brian Bui
- Department of Physics, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Jian Yang
- Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA
| | - Eric Amador
- Department of Physics, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Mingli Chen
- Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang 110819, China
| | - Christina Xing
- Department of Physics, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Aseem Atul Athavale
- Department of Materials Science and Engineering, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Yaowu Hao
- Department of Materials Science and Engineering, The University of Texas at Arlington, Arlington, TX 76019, USA
| | - Wirya Feizi
- Department of Physics, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, USA
| | - Lloyd Lumata
- Department of Physics, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, USA
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Zhu F, Wang BR, Zhu ZF, Wang SQ, Chai CX, Shang D, Li M. Photodynamic therapy: A next alternative treatment strategy for hepatocellular carcinoma? World J Gastrointest Surg 2021; 13:1523-1535. [PMID: 35070061 PMCID: PMC8727193 DOI: 10.4240/wjgs.v13.i12.1523] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/20/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is one of the most common cancers in the world. Of all types of liver cancer, hepatocellular carcinoma (HCC) is known to be the most frequent primary liver malignancy and has seriously compromised the health status of the general population. Locoregional thermal ablation techniques such as radiofrequency and microwave ablation, have attracted attention in clinical practice as an alternative strategy for HCC treatment. However, their aggressive thermal effect may cause undesirable complications such as hepatic decompensation, hemorrhage, bile duct injury, extrahepatic organ injuries, and skin burn. In recent years, photodynamic therapy (PDT), a gentle locoregional treatment, has attracted attention in ablation therapy for patients with superficial or luminal tumors as an alternative treatment strategy. However, some inherent defects and extrinsic factors of PDT have limited its use in clinical practice for deep-seated HCC. In this contribution, the aim is to summarize the current status and challenges of PDT in HCC treatment and provide potential strategies to overcome these deficiencies in further clinical translational practice.
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Affiliation(s)
- Feng Zhu
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Bi-Rong Wang
- Department of Breast and Thyroid Surgery, Wuhan Fourth Hospital (Puai Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zheng-Feng Zhu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Si-Qin Wang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Chu-Xing Chai
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Dan Shang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Perrier S, Yang J, Yu X, Song JI, Song Q, Hall SCL, Yu G. AIE Featured Supramolecular Tubisomes for Imaging-Guided Drug Delivery. Angew Chem Int Ed Engl 2021; 61:e202115208. [PMID: 34927320 DOI: 10.1002/anie.202115208] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Indexed: 11/07/2022]
Abstract
Polymeric cylinders, a fascinating type of nanostructures with high surface area, internal volume and rigidity, have been exploited as novel drug delivery vehicles over the past decade. However, it's still an open challenge to afford cylindrical nanostructures using polymeric building blocks via traditional self-assembly processes. Herein, we report a hierarchical self-assembly strategy of preparing cylindrical aggregates (tubisomes) from an amphiphilic supramolecular bottlebrush polymer in which cyclic peptide nanotube is employed as the noncovalent backbone. Additionally, aggregation induced emission effect was introduced into the tubisomes to endow them with excellent fluorescent property. Intriguingly, encapsulation of anticancer drug doxorubicin (DOX) can inactivate the fluorescence of both tubisome and DOX due to the energy transfer relay (ETR). The release of DOX can interrupt the ETR effect and light up the silenced fluorescence, thereby permitting the in-situ visualization of drug release. The supramolecular tubisomes described here paves an alternative way for fabricating polymeric cylindrical nanostructures, and holds great potential in imaging-guided drug delivery.
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Affiliation(s)
- Sebastien Perrier
- The University of Warwick / Monash University, Department of Chemistry, Library Road, CV4 7AL, Coventry, UNITED KINGDOM
| | - Jie Yang
- Nanjing Forestry University, College of Science, 210037, Nanjing, CHINA
| | - Xinyang Yu
- Tsinghua University, Department of Chemistry, CHINA
| | - Ji-Inn Song
- University of Warwick, Department of Chemistry, UNITED KINGDOM
| | - Qiao Song
- University of Warwick, Department of Chemistry, UNITED KINGDOM
| | | | - Guocan Yu
- Tsinghua University, Department of Chemistry, CHINA
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Zha M, Yang G, Li Y, Zhang C, Li B, Li K. Recent Advances in AIEgen-Based Photodynamic Therapy and Immunotherapy. Adv Healthc Mater 2021; 10:e2101066. [PMID: 34519181 DOI: 10.1002/adhm.202101066] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/20/2021] [Indexed: 12/13/2022]
Abstract
Cancer, one of the leading causes of death, has seriously threatened public health. However, there is still a lack of effective treatments. Nowadays, photodynamic therapy (PDT), relying on photosensitizers to trigger the generation of reactive oxygen species (ROS) for killing cancer cells, has been emerging as a noninvasive anti-cancer strategy. To enhance the overall anti-cancer efficacy of PDT, various approaches including molecular design and combination with other therapeutic techniques have been proposed and implemented. Especially, photodynamic immunotherapy that can effectively evoke the body's immune response has attracted much attention. Recently, a class of photosensitizers with aggregation-induced emission (AIE) character have shown unique promises, taking advantage of their profound fluorescence and ROS-generating ability in the aggregation state. Despite the promising results demonstrated by several groups, the associated studies are few and the mechanism of such AIEgen-based photodynamic immunotherapy has not been fully understood. This review discusses the recent advances in the AIEgen-based enhanced PDT with a special focus on the AIE photosensitizers for photodynamic immunotherapy, aiming to inspire more opportunities for in-depth investigation of the working principles in this emerging anti-cancer approach.
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Affiliation(s)
- Menglei Zha
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering Southern University of Science and Technology (SUSTech) No. 1088 Xueyuan Rd. Shenzhen Guangdong 518055 P. R. China
| | - Guang Yang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering Southern University of Science and Technology (SUSTech) No. 1088 Xueyuan Rd. Shenzhen Guangdong 518055 P. R. China
| | - Yaxi Li
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering Southern University of Science and Technology (SUSTech) No. 1088 Xueyuan Rd. Shenzhen Guangdong 518055 P. R. China
| | - Chen Zhang
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering Southern University of Science and Technology (SUSTech) No. 1088 Xueyuan Rd. Shenzhen Guangdong 518055 P. R. China
| | - Bo Li
- Department of Cardiology Shandong University Central Hospital of Zibo NO.10 South Shanghai Road Zibo 255000 China
| | - Kai Li
- Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering Southern University of Science and Technology (SUSTech) No. 1088 Xueyuan Rd. Shenzhen Guangdong 518055 P. R. China
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Dai J, Dong X, Wang Q, Lou X, Xia F, Wang S. PEG-Polymer Encapsulated Aggregation-Induced Emission Nanoparticles for Tumor Theranostics. Adv Healthc Mater 2021; 10:e2101036. [PMID: 34414687 DOI: 10.1002/adhm.202101036] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/28/2021] [Indexed: 12/15/2022]
Abstract
In the field of tumor imaging and therapy, the aggregation-caused quenching (ACQ) effect of fluorescent dyes at high concentration is a great challenge. In this regard, the aggregation-induced emission luminogens (AIEgens) show great potential, since AIEgens effectively overcome the ACQ effect and have better fluorescence quantum yield, photobleaching resistance, and photosensitivity. Polyethylene glycol (PEG)-polymer is the most commonly used carrier to prepare nanoparticles (NPs). The advantage of PEGylation is that it can greatly prolong the metabolic half-life and reduce immunogenicity and toxicity. Considering that the hydrophobicity of most AIEgens hinders their application in organisms, the use of PEG-polymer encapsulation is an effective strategy to overcome this obstacle. Importantly, bioactive functional groups can be modified on PEG-polymers to enhance the biological effect of NPs. The combination of powerful AIEgens and PEG-polymers provides a new strategy for tumor imaging and therapy, which is promising for clinical application.
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Affiliation(s)
- Jun Dai
- Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology 1095 Jiefang Avenue Wuhan 430032 China
| | - Xiaoqi Dong
- State Key Laboratory of Biogeology and Environmental Geology Faculty of Materials Science and Chemistry China University of Geosciences 388 Lumo Road Wuhan 430074 China
| | - Quan Wang
- State Key Laboratory of Biogeology and Environmental Geology Faculty of Materials Science and Chemistry China University of Geosciences 388 Lumo Road Wuhan 430074 China
| | - Xiaoding Lou
- State Key Laboratory of Biogeology and Environmental Geology Faculty of Materials Science and Chemistry China University of Geosciences 388 Lumo Road Wuhan 430074 China
| | - Fan Xia
- State Key Laboratory of Biogeology and Environmental Geology Faculty of Materials Science and Chemistry China University of Geosciences 388 Lumo Road Wuhan 430074 China
| | - Shixuan Wang
- Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology 1095 Jiefang Avenue Wuhan 430032 China
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Ma J, Chen Y, Liang W, Li L, Du J, Pan C, Zhang C. ROS-responsive dimeric prodrug-based nanomedicine targeted therapy for gastric cancer. Drug Deliv 2021; 28:1204-1213. [PMID: 34142633 PMCID: PMC8218932 DOI: 10.1080/10717544.2021.1937380] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/24/2021] [Accepted: 05/25/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) remains a major public health problem. Ursolic acid (UA) is reported to be effective in inhibiting GC; however, its low solubility and poor biocompatibility have greatly hindered its clinical application. Herein, an innovative reactive oxygen species (ROS)-sensitive UA dimeric prodrug is developed by coupling two UA molecules via a ROS-cleavable linkage, which can self-assemble into stable nanoparticles in the presence of surfactant. This new UA-based delivery system comprises the following major components: (I) dimeric prodrug inner core that can achieve high drug-loading (55%, w/w) and undergo rapid and selective conversion into intact drug molecules in response to ROS; (II) a polyethylene glycol (PEG) shell to improve colloid stability and extend blood circulation, and (III) surface-modified internalizing RGD (iRGD) to increase tumor targeting. Enhancement of the antitumor effect of this delivery system was demonstrated against GC tumors in vitro and in vivo. This novel approach offers the potential for clinical applications of UA.
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Affiliation(s)
- Jiachi Ma
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Yuzhong Chen
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Wanqing Liang
- Bengbu Medical College, Bengbu, People's Republic of China
| | - Lei Li
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Jun Du
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Chengwu Pan
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
| | - Chensong Zhang
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China
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Wang D, Kuzma ML, Tan X, He TC, Dong C, Liu Z, Yang J. Phototherapy and optical waveguides for the treatment of infection. Adv Drug Deliv Rev 2021; 179:114036. [PMID: 34740763 PMCID: PMC8665112 DOI: 10.1016/j.addr.2021.114036] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 10/11/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023]
Abstract
With rapid emergence of multi-drug resistant microbes, it is imperative to seek alternative means for infection control. Optical waveguides are an auspicious delivery method for precise administration of phototherapy. Studies have shown that phototherapy is promising in fighting against a myriad of infectious pathogens (i.e. viruses, bacteria, fungi, and protozoa) including biofilm-forming species and drug-resistant strains while evading treatment resistance. When administered via optical waveguides, phototherapy can treat both superficial and deep-tissue infections while minimizing off-site effects that afflict conventional phototherapy and pharmacotherapy. Despite great therapeutic potential, exact mechanisms, materials, and fabrication designs to optimize this promising treatment option are underexplored. This review outlines principles and applications of phototherapy and optical waveguides for infection control. Research advances, challenges, and outlook regarding this delivery system are rigorously discussed in a hope to inspire future developments of optical waveguide-mediated phototherapy for the management of infection and beyond.
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Affiliation(s)
- Dingbowen Wang
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Michelle Laurel Kuzma
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Xinyu Tan
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Academy of Orthopedics, Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province 510280, China
| | - Tong-Chuan He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Cheng Dong
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Zhiwen Liu
- Department of Electrical Engineering, Materials Research Institute, The Pennsylvania State University, University Park, PA 16802, USA
| | - Jian Yang
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
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Xu J, Zheng Q, Cheng X, Hu S, Zhang C, Zhou X, Sun P, Wang W, Su Z, Zou T, Song Z, Xia Y, Yi X, Gao Y. Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma. J Nanobiotechnology 2021; 19:355. [PMID: 34717654 PMCID: PMC8557521 DOI: 10.1186/s12951-021-01101-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 10/20/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. METHODS A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. RESULTS The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. CONCLUSION Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC.
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Affiliation(s)
- Jianjun Xu
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qichang Zheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiang Cheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shaobo Hu
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chen Zhang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xing Zhou
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ping Sun
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Weimin Wang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhe Su
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tianhao Zou
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zifang Song
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yun Xia
- Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiaoqing Yi
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, College of Pharmacy, Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Gannan Medical University, Ganzhou, 341000, China.
| | - Yang Gao
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Li B, Wang D, Lee MMS, Wang W, Tan Q, Zhao Z, Tang BZ, Huang X. Fabrics Attached with Highly Efficient Aggregation-Induced Emission Photosensitizer: Toward Self-Antiviral Personal Protective Equipment. ACS NANO 2021; 15:13857-13870. [PMID: 34313425 DOI: 10.1021/acsnano.1c06071] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Personal protective equipment (PPE) is vital for the prevention and control of SARS-CoV-2. However, conventional PPEs lack virucidal capabilities and arbitrarily discarding used PPEs may cause a high risk for cross-contamination and environmental pollution. Recently reported photothermal or photodynamic-mediated self-sterilizing masks show bactericidal-virucidal abilities but have some inherent disadvantages, such as generating unbearable heat during the photothermal process or requiring additional ultraviolet light irradiation to inactivate pathogens, which limit their practical applications. Here, we report the fabrication of a series of fabrics (derived from various PPEs) with real-time self-antiviral capabilities, on the basis of a highly efficient aggregation-induced emission photosensitizer (namely, ASCP-TPA). ASCP-TPA possesses facile synthesis, excellent biocompatibility, and extremely high reactive oxygen species generation capacity, which significantly outperforms the traditional photosensitizers. Meanwhile, the ASCP-TPA-attached fabrics (ATaFs) show tremendous photodynamic inactivation effects against MHV-A59, a surrogate coronavirus of SARS-CoV-2. Upon ultralow-power white light irradiation (3.0 mW cm-2), >99.999% virions (5 log) on the ATaFs are eliminated within 10 min. Such ultralow-power requirement and rapid virus-killing ability enable ATaFs-based PPEs to provide real-time protection for the wearers under indoor light irradiation. ATaFs' virucidal abilities are retained after 100 washings or continuous exposure to office light for 2 weeks, which offers the benefits of reusability and long-term usability. Furthermore, ATaFs show no toxicity to normal skin, even upon continuous high-power light illumination. This self-antiviral ATaFs-based strategy may also be applied to fight against other airborne pathogens and holds huge potential to alleviate global PPE supply shortages.
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Affiliation(s)
- Bin Li
- Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
- Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai 519000, Guangdong, China
- Key Laboratory of Tropical Diseases Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
| | - Dong Wang
- Center for AIE Research, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, Guangdong, China
- Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 999077, Hong Kong, China
| | - Michelle M S Lee
- Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 999077, Hong Kong, China
| | - Wei Wang
- Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
| | - Qingqin Tan
- Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
| | - Zhaoyan Zhao
- Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
| | - Ben Zhong Tang
- Center for AIE Research, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, Guangdong, China
- Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 999077, Hong Kong, China
| | - Xi Huang
- Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
- Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai 519000, Guangdong, China
- Key Laboratory of Tropical Diseases Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
- The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, Guangdong, China
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Saini V, Venkatesh V. AIE material for photodynamic therapy. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2021; 185:45-73. [PMID: 34782107 DOI: 10.1016/bs.pmbts.2021.06.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Photodynamic therapy (PDT) is emerging as an excellent strategy to treat different types of cancers. The advantages of using PDT over other cancer treatment modalities are owing to its non-invasive nature, spatiotemporal precession, controllable photoactivity, and least side effects. The photosensitization ability of traditional photosensitizers (PSs) are severely curtailed by aggregation-induced quenching (ACQ). On the contrary, aggregation induced emission (AIE) molecules/fluorogens (AIEgens) show enhanced fluorescence emission and high reactive oxygen species (ROS)/singlet oxygen (1O2) production capability in the aggregated state. These unique characteristics of AIEgens make them potential AIE-PSs for fluorescence/luminescence image-guided combination PDT. In this chapter, we discussed the strategies that are developed to synthesize small molecule-based AIE-PSs, metal complex-based AIE-PSs, and AIE-PSs with two-photon absorbance (TPA) properties, polymer-based AIE-PSs, and nanoparticles based AIE-PSs for PDT. We have also discussed the rational design of targeting peptide conjugated AIE-PSs to selective target cancer cells over normal cells. Furthermore, recent findings on nanoparticle-based combination AIE-PSs are also discussed, where the combination AIE-PSs show synergistically improved anticancer activity and overcome the drug resistance. Finally, we shed light on the recent development, ongoing challenges, and future directions for designing better AIE-PS for PDT.
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Affiliation(s)
- Vishal Saini
- Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
| | - V Venkatesh
- Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India.
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Huang L, Asghar S, Zhu T, Ye P, Hu Z, Chen Z, Xiao Y. Advances in chlorin-based photodynamic therapy with nanoparticle delivery system for cancer treatment. Expert Opin Drug Deliv 2021; 18:1473-1500. [PMID: 34253129 DOI: 10.1080/17425247.2021.1950685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Introduction: The treatment of tumors is one of the most difficult problems in the medical field at present. Patients often use a comprehensive therapy that combines surgery, radiotherapy, and chemotherapy. Photodynamic therapy (PDT) has prominent potential for eradicating various cancers. Chlorin-based photosensitizers (PSs), as one of the most utilized photosensitizers, have many advantages over conventional photosensitizers; however, a successful chlorin-based PDT needs multi-functional nano-carriers for selective photosensitizer delivery. The number of researches about nanoparticles designed for improved chlorin-based PSs is increasing in the current era. In this article, we give a brief review focused on the recent research progress in design of chlorin-based nanoparticles for the treatment of malignant tumors with photodynamic therapy.Areas covered: This review focuses on the current nanoparticle platforms for PDT, and describes different strategies to achieve controllable PDT by chlorin-nano-delivery systems. The challenges and prospects of PDT in clinical applications are also discussed.Expert opinions: The requirement for PDT to eradicate cancers has increased exponentially in recent years. The major clinically used photosensitizers are hydrophobic. The main obstacles in effective delivery of PSs are associated with this intrinsic nature. The design of nano-delivery systems to load PSs is pivotal for PSs' widespread use.
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Affiliation(s)
- Lin Huang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China
| | - Sajid Asghar
- Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Ting Zhu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China
| | - Panting Ye
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China
| | - Ziyi Hu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China
| | - Zhipeng Chen
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China.,Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanyu Xiao
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR, China
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Zheng Y, Zhang Z, Liu Q, Wang Y, Hao J, Kang Z, Wang C, Zhao X, Liu Y, Shi L. A near-infrared light-excitable immunomodulating nano-photosensitizer for effective photoimmunotherapy. Biomater Sci 2021; 9:4191-4198. [PMID: 33982683 DOI: 10.1039/d1bm00569c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Photodynamic therapy has great potential for tumor ablation and the activation of antitumor immune responses. However, its overall therapeutic efficiency is often limited by the immunosuppressive tumor microenvironment. We developed a near-infrared light-excitable immunomodulating nano-photosensitizer (NeINP) that can improve reactive oxygen species production and regulate the immunosuppressive TME to improve photoimmunotherapy. The NeINP is composed of a photosensitive core and a pH-responsive polymer shell, which allows for NeINP loading and delivery of small-molecular immunomodulators to tumor sites for regulation of the immunosuppressive TME and effective photoimmunotherapy. Through the co-delivery of celecoxib and the NIR-triggered photodynamic core to tumors, the NeINP was shown to regulate the immunosuppressive TME and enhance antitumor immunity, leading to the elimination of residual tumor and reduction of metastasis and recurrence. The NeINP can be optimized to co-deliver other immunomodulators, and thus has potential as a universal platform for efficient, precise photoimmunotherapy.
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Affiliation(s)
- Yadan Zheng
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Zhanzhan Zhang
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Qi Liu
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Ying Wang
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Jialei Hao
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Ziyao Kang
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Chun Wang
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Xinzhi Zhao
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Yang Liu
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
| | - Linqi Shi
- Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
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Zhang Q, Zhang J, Song J, Liu Y, Ren X, Zhao Y. Protein-Based Nanomedicine for Therapeutic Benefits of Cancer. ACS NANO 2021; 15:8001-8038. [PMID: 33900074 DOI: 10.1021/acsnano.1c00476] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Proteins, a type of natural biopolymer that possess many prominent merits, have been widely utilized to engineer nanomedicine for fighting against cancer. Motivated by their ever-increasing attention in the scientific community, this review aims to provide a comprehensive showcase on the current landscape of protein-based nanomedicine for cancer therapy. On the basis of role differences of proteins in nanomedicine, protein-based nanomedicine engineered with protein therapeutics, protein carriers, enzymes, and composite proteins is introduced. The cancer therapeutic benefits of the protein-based nanomedicine are also discussed, including small-molecular therapeutics-mediated therapy, macromolecular therapeutics-mediated therapy, radiation-mediated therapy, reactive oxygen species-mediated therapy, and thermal effect-mediated therapy. Lastly, future developments and potential challenges of protein-based nanomedicine are elucidated toward clinical translation. It is believed that protein-based nanomedicine will play a vital role in the battle against cancer. We hope that this review will inspire extensive research interests from diverse disciplines to further push the developments of protein-based nanomedicine in the biomedical frontier, contributing to ever-greater medical advances.
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Affiliation(s)
- Qiuhong Zhang
- International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China
- College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
| | - Junmin Zhang
- International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China
| | - Jun Song
- College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China
| | - Yizhen Liu
- International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China
| | - Xiangzhong Ren
- International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China
| | - Yanli Zhao
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore
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Exploiting a New Approach to Destroy the Barrier of Tumor Microenvironment: Nano-Architecture Delivery Systems. Molecules 2021; 26:molecules26092703. [PMID: 34062992 PMCID: PMC8125456 DOI: 10.3390/molecules26092703] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/25/2021] [Accepted: 04/29/2021] [Indexed: 01/04/2023] Open
Abstract
Recent findings suggest that tumor microenvironment (TME) plays an important regulatory role in the occurrence, proliferation, and metastasis of tumors. Different from normal tissue, the condition around tumor significantly altered, including immune infiltration, compact extracellular matrix, new vasculatures, abundant enzyme, acidic pH value, and hypoxia. Increasingly, researchers focused on targeting TME to prevent tumor development and metastasis. With the development of nanotechnology and the deep research on the tumor environment, stimulation-responsive intelligent nanostructures designed based on TME have attracted much attention in the anti-tumor drug delivery system. TME-targeted nano therapeutics can regulate the distribution of drugs in the body, specifically increase the concentration of drugs in the tumor site, so as to enhance the efficacy and reduce adverse reactions, can utilize particular conditions of TME to improve the effect of tumor therapy. This paper summarizes the major components and characteristics of TME, discusses the principles and strategies of relevant nano-architectures targeting TME for the treatment and diagnosis systematically.
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Lima PHCD, Butera AP, Cabeça LF, Ribeiro-Viana RM. Liposome surface modification by phospholipid chemical reactions. Chem Phys Lipids 2021; 237:105084. [PMID: 33891960 DOI: 10.1016/j.chemphyslip.2021.105084] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/17/2021] [Accepted: 04/16/2021] [Indexed: 12/13/2022]
Abstract
Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug delivery, diagnosis, and in many other academic areas. A novel class of this nanoparticle is the actively target liposome, which is constructed with the surface modified with appropriated molecules (or ligands) to actively bind a target molecule of certain cells, system, or tissue. There are many ways to functionalize these nanostructures, from non-covalent adsorption to covalent bond formation. In this review, we focus on the strategies of modifying liposomes by glycerophospholipid covalent chemical reaction. The approach used in this text summarizes the main reactions and strategies used in phospholipid modification that can be carried out by chemists and researchers from other areas. The knowledge of these methodologies is of great importance for planning new studies using this material and also for manipulating its properties.
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Affiliation(s)
- Pedro Henrique Correia de Lima
- Programa de Pós-graduação em Ciências e Engenharia de Materiais (PPGCEM-UTFPR), Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil
| | - Anna Paola Butera
- Departamento de Química, Universidade Estadual de Londrina, UEL, CEP 86051-980, Londrina, PR, Brazil
| | - Luis Fernando Cabeça
- Programa de Pós-graduação em Ciências e Engenharia de Materiais (PPGCEM-UTFPR), Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil; Departamento Acadêmico de Química, Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil
| | - Renato Márcio Ribeiro-Viana
- Programa de Pós-graduação em Ciências e Engenharia de Materiais (PPGCEM-UTFPR), Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil; Departamento Acadêmico de Química, Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil.
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Han W, Du Y, Song M, Sun K, Xu B, Yan F, Tian W. Fluorescent nanorods based on 9,10-distyrylanthracene (DSA) derivatives for efficient and long-term bioimaging. J Mater Chem B 2021; 8:9544-9554. [PMID: 33000780 DOI: 10.1039/c9tb02883h] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Fluorescent nanoparticles based on 9,10-distyrylanthracene (DSA) derivatives (4,4'-((1E,1'E)-anthracene-9,10-diylbis(ethene-2,1-diyl))bis(N,N-dimethylaniline) (NDSA) and 4,4'-((1E,1'E)-anthracene-9,10-diylbis(ethene-2,1-diyl))dibenzonitrile (CNDSA)) were prepared using an ultrasound aided nanoprecipitation method. The morphologies of the fluorescent nanoparticles could be controlled by adjusting the external ultrasonication time. NDSA or CNDSA could form spherical nanodots (NDSA NDs, CNDSA NDs) in a THF-H2O mixture with an 80% or 70% water fraction when the ultrasonication time was 30 s. When the ultrasonication time was prolonged to 10 min, NDSA and CNDSA could assemble into nanorods (NDSA NRs, CNDSA NRs). Meanwhile, the sizes of NDSA NRs and CNDSA NRs could be controlled by adjusting the water content in the mixture. As the water fraction was increased from 60% to 80%, the sizes of NDSA and CNDSA nanorods or nanodots reduced from 238.4 nm to 140.3 nm, and 482 nm to 198.4 nm, respectively. When the water fraction was up to 90%, irregular morphologies of NDSA and CNDSA could be observed. The nanoparticles exhibited intense fluorescence emission, good anti-photobleaching properties, as well as excellent stability and biocompatibility. In vitro cell imaging experiments indicated that the nanorods prepared by this simple method had the potential to be used for efficient and noninvasive long-term bioimaging.
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Affiliation(s)
- Wenkun Han
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
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Alam P, Leung NL, Zhang J, Kwok RT, Lam JW, Tang BZ. AIE-based luminescence probes for metal ion detection. Coord Chem Rev 2021. [DOI: 10.1016/j.ccr.2020.213693] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Li X, Zhao Y, Zhang T, Xing D. Mitochondria-Specific Agents for Photodynamic Cancer Therapy: A Key Determinant to Boost the Efficacy. Adv Healthc Mater 2021; 10:e2001240. [PMID: 33236531 DOI: 10.1002/adhm.202001240] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/02/2020] [Indexed: 02/06/2023]
Abstract
Mitochondria-targeted photodynamic therapy (Mt-PDT), which enables the photogenerated cytotoxic oxygen species with fatal oxidative damage to block mitochondrial functions, has been considered as a promising method to enhance the anticancer effectiveness. Aiming at the challenges of PDT, in the past few decades, numerous mitochondria-targeting molecular agents have been developed to boost the PDT efficacy via directly destroying the mitochondria or activating mitochondria-mediated cell death pathways. Herein, a review for recent advances of Mt-PDT is highlighted including: mitochondrial targeting design principles and strategies, therapeutic performance of mitochondria-targeted agents-mediated PDT as well as the agent-free Mt-PDT. In addition, it puts together the achievements of the combinatory mitochondria-anchoring PDT and other anticancer strategies, demonstrating the advantages provided by Mt-PDT. The existing challenges are discussed and future settlements for the development of mitochondria-specific agents are also forecasted.
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Affiliation(s)
- Xipeng Li
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
- Guangdong Provincial Key Laboratory of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
| | - Yu Zhao
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
- Guangdong Provincial Key Laboratory of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
| | - Tao Zhang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
- Guangdong Provincial Key Laboratory of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
| | - Da Xing
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
- Guangdong Provincial Key Laboratory of Laser Life Science College of Biophotonics South China Normal University Guangzhou 510631 P. R. China
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Sakamaki Y, Ozdemir J, Heidrick Z, Azzun A, Watson O, Tsuji M, Salmon C, Sinha A, Batta-Mpouma J, McConnell Z, Fugitt D, Du Y, Kim JW, Beyzavi H. A Bio-Conjugated Chlorin-Based Metal-Organic Framework for Targeted Photodynamic Therapy of Triple Negative Breast and Pancreatic Cancers. ACS APPLIED BIO MATERIALS 2021; 4:1432-1440. [PMID: 34337346 DOI: 10.1021/acsabm.0c01324] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The field of photodynamic therapy (PDT) has continued to show promise as a potential method for treating tumors. In this work a photosensitizer (PS) has been delivered to cancer cell lines for PDT by incorporation into the metal-organic framework (MOF) as an organic linker. By functionalizing the surface of MOF nanoparticles with maltotriose the PS can efficiently target cancer cells with preferential uptake into pancreatic and breast cancer cell lines. Effective targeting overcomes some current problems with PDT including long-term photosensitivity and tumor specificity. Developing a PS with optimal absorption and stability is one of the foremost challenges in PDT and the synthesis of a chlorin which is activated by long-wavelength light and is resistant to photo-bleaching is described. This chlorin-based MOF shows anti-cancer ability several times higher than that of porphyrin-based MOFs with little toxicity to normal cell lines and no dark toxicity.
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Affiliation(s)
- Yoshie Sakamaki
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - John Ozdemir
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Zachary Heidrick
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Anthony Azzun
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Olivia Watson
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Miu Tsuji
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Christopher Salmon
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Arvind Sinha
- Department of Biological and Agricultural Engineering and Institute for Nanoscience and Engineering University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Joseph Batta-Mpouma
- Department of Biological and Agricultural Engineering and Institute for Nanoscience and Engineering University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Zachary McConnell
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - David Fugitt
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Yuchun Du
- Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Jin-Woo Kim
- Department of Biological and Agricultural Engineering and Institute for Nanoscience and Engineering University of Arkansas, Fayetteville, Arkansas 72701, United States
| | - Hudson Beyzavi
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
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