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Yang F, Wang L, Wang H, Zhang S, Li Y. Perspectives on photodynamic therapy combined with immunotherapy in treatment of colorectal cancer: An overview based on experimental studies. Photodiagnosis Photodyn Ther 2025; 52:104464. [PMID: 39746558 DOI: 10.1016/j.pdpdt.2024.104464] [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: 06/09/2024] [Revised: 12/16/2024] [Accepted: 12/27/2024] [Indexed: 01/04/2025]
Abstract
Colorectal cancer (CRC) is one of the major cancers threatening human health, with high mortality, tumor drug resistance and metastasis. Due to its advantages of non-invasive, strongly targeted and limited side effects, Photodynamic therapy (PDT) has become a promising treatment for CRC. Remarkably, PDT has been shown to activate T cell-adaptive immune response and induce immunogenic cell death (ICD). Used in combination with other treatment techniques, PDT has considerable promise in the management of colorectal cancer. In particular, the combination of PDT and tumor immunotherapy, the systemic anti-tumor immune response was enhanced more significantly. This strategy is expected to achieve a synergistic anti-tumor effect by inducing tumor cell apoptosis, regulating tumor immune microenvironment and effectively activating anti-tumor immunity during treatment process. This review focuses on the research of PDT combined with immunotherapy to improve the treatment of CRC. In most studies, a positive effect was observed for combination therapy, experimentally indicating new therapeutic opportunities for CRC.
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Affiliation(s)
- Fang Yang
- Medical College, Guangxi University, Nanning 530004, Guangxi, China
| | - Li Wang
- Medical College, Guangxi University, Nanning 530004, Guangxi, China
| | - Haiping Wang
- Cancer Institute, School of Medicine, Jianghan University, Wuhan, China
| | - Song Zhang
- Department of Gastroenterology, General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China.
| | - Yixiang Li
- Medical College, Guangxi University, Nanning 530004, Guangxi, China.
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2
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Jin Z, Li Y, Yi H, Wang M, Wang C, Du S, Zeng W, Zong Z. Pathogenetic development, diagnosis and clinical therapeutic approaches for liver metastasis from colorectal cancer (Review). Int J Oncol 2025; 66:22. [PMID: 39950314 PMCID: PMC11844340 DOI: 10.3892/ijo.2025.5728] [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: 08/13/2024] [Accepted: 01/10/2025] [Indexed: 02/23/2025] Open
Abstract
Colorectal cancer (CRC) is a prevalent malignancy and a significant proportion of patients with CRC develop liver metastasis (CRLM), which is a major contributor to CRC‑related mortality. The present review aimed to comprehensively examine the pathogenetic development and diagnosis of CRLM and the clinical therapeutic approaches for treatment of this disease. The molecular mechanisms underlying CRLM were discussed, including the role of the tumour microenvironment and epithelial‑mesenchymal transition. The present review also highlighted the importance of early detection and the current challenges in predicting the development of CRLM. Various treatment strategies were reviewed, including surgical resection, chemotherapy and immunotherapy, and the potential of novel therapies, such as selective internal radiation therapy and Traditional Chinese Medicine. Despite recent advancements in treatment options, the treatment of CRLM remains a therapeutic challenge due to the complexity of the liver microenvironment and the heterogeneity of CRC. The present review emphasized the need for a multidisciplinary approach and the integration of emerging therapies to improve patient outcomes.
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Affiliation(s)
- Zhenhua Jin
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Yin Li
- Huan Kui Academy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Hao Yi
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Menghui Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Huan Kui Academy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Chaofeng Wang
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Shaokun Du
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Wenjuan Zeng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Huan Kui Academy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Zhen Zong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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Rodrigues JA, Correia JH. Photodynamic Therapy for Colorectal Cancer: An Update and a Look to the Future. Int J Mol Sci 2023; 24:12204. [PMID: 37569580 PMCID: PMC10418644 DOI: 10.3390/ijms241512204] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/24/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
This review provides an update on the current state of photodynamic therapy (PDT) for colorectal cancer (CRC) and explores potential future directions in this field. PDT has emerged as a promising minimally invasive treatment modality that utilizes photosensitizers and specific light wavelengths to induce cell death in targeted tumor tissues. In recent years, significant progress has been made in understanding the underlying mechanisms, optimizing treatment protocols, and improving the efficacy of PDT for CRC. This article highlights key advancements in PDT techniques, including novel photosensitizers, light sources, and delivery methods. Furthermore, it discusses ongoing research efforts and potential future directions, such as combination therapies and nanotechnology-based approaches. By elucidating the current landscape and providing insights into future directions, this review aims to guide researchers and clinicians in harnessing the full potential of PDT for the effective management of CRC.
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Affiliation(s)
- José A. Rodrigues
- CMEMS-UMinho, University of Minho, 4800-058 Guimarães, Portugal;
- LABBELS—Associate Laboratory, 4800-122 Braga, Portugal
| | - José H. Correia
- CMEMS-UMinho, University of Minho, 4800-058 Guimarães, Portugal;
- LABBELS—Associate Laboratory, 4800-122 Braga, Portugal
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Robinson TP, Pebror T, Krosin ME, Koniaris LG. Ablative Therapy in Non-HCC Liver Malignancy. Cancers (Basel) 2023; 15:cancers15041200. [PMID: 36831543 PMCID: PMC9954041 DOI: 10.3390/cancers15041200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
Surgical extirpation of liver tumors remains a proven approach in the management of metastatic tumors to the liver, particularly those of colorectal origin. Ablative, non-resective therapies are an increasingly attractive primary therapy for liver tumors as they are generally better tolerated and result in far less morbidity and mortality. Ablative therapies preserve greater normal liver parenchyma allowing better post-treatment liver function and are particularly appropriate for treating subsequent liver-specific tumor recurrence. This article reviews the current status of ablative therapies for non-hepatocellular liver tumors with a discussion of many of the clinically available approaches.
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Affiliation(s)
- Tyler P. Robinson
- Department of Surgery, Indiana University, Indianapolis, IN 46202, USA
- Correspondence: ; Tel.: +1-312-371-8360
| | - Travis Pebror
- Department of Interventional Radiology, Indiana University, Indianapolis, IN 46202, USA
| | - Matthew E. Krosin
- Department of Interventional Radiology, Indiana University, Indianapolis, IN 46202, USA
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Frant MP, Trytek M, Paduch R. Assessing the In Vitro Activity of Selected Porphyrins in Human Colorectal Cancer Cells. Molecules 2022; 27:molecules27062006. [PMID: 35335367 PMCID: PMC8955395 DOI: 10.3390/molecules27062006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/12/2022] [Accepted: 03/17/2022] [Indexed: 11/16/2022] Open
Abstract
Standard in vitro analyses determining the activity of different compounds included in the chemotherapy of colon cancer are currently insufficient. New ideas, such as photodynamic therapy (PDT), may bring tangible benefits. The aim of this study was to show that the biological activity of selected free-base and manganese (III) metallated porphyrins differs in the limitation of colon cancer cell growth in vitro. White light irradiation was also hypothesized to initiate a photodynamic effect on tested porphyrins. Manganese porphyrin (>1 μM) significantly decreased the viability of the colon tumor and normal colon epithelial cells, both in light/lack of light conditions, while decreasing a free-base porphyrin after only 3 min of white light irradiation. Both porphyrins interacted with cytostatics in an antagonistic manner. The manganese porphyrin mainly induced apoptosis and necrosis in the tumor, and apoptosis in the normal cells, regardless of light exposure conditions. The free-base porphyrin conducted mainly apoptosis and autophagy. Normal and tumor cells released low levels of IL-1β and IL-10. Tumor cells released a low level of IL-6. Light conditions and porphyrins were influenced at the cytokine level. Tested manganese (III) metallated and free-base porphyrins differ in their activity against human colon cancer cells. The first showed no photodynamic, but a toxic activity, whereas the second expressed high photodynamic action. White light use may induce a photodynamic effect associated with porphyrins.
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Affiliation(s)
- Maciej Piotr Frant
- Department of Swine Diseases, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, Poland;
| | - Mariusz Trytek
- Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, 20-033 Lublin, Poland;
| | - Roman Paduch
- Department of Virology and Immunology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, Chmielna 1, 20-079 Lublin, Poland
- Correspondence: or
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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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Al-Sarraj F. The effect of antibiotics and photodynamic therapy on extended-spectrum beta-lactamase (ESBL) positive of Escherichia coli and Klebsiella pneumoniae in urothelial cells. Saudi J Biol Sci 2021; 28:5561-5567. [PMID: 34588866 PMCID: PMC8459124 DOI: 10.1016/j.sjbs.2021.05.074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 05/25/2021] [Accepted: 05/27/2021] [Indexed: 01/10/2023] Open
Abstract
Background/aim Urinary tract infections are commonly caused by the bacteria Escherichia coli and Klebsiella pneumoniae (UTI). The emergence of extended-spectrum -lactamase (ESBL)-producing bacteria strains has made UTI treatment more difficult. Materials and methods The aim of this study was to characterize E. coli and K. pneumoniae strains' cytotoxic effects, antibiotic sensitivity, interaction with urothelial cells, and reaction to photodynamic therapy. Results As demonstrated by the higher number of colonies formed, the ESBL + E. coli and K. Pneumonia showed a higher degree of binding with human urothelial cells. With the urothelial cells, K. Pneumonia had the highest binding ability. The cytotoxicity of non-ESBL generating E. coli and K. Pneumonia, on the other hand, was higher. With longer incubation, the discrepancy between the cytotoxic effects of non-ESBL producer and ESBL + E. coli decreased. K. Pneumonia was the opposite. The concentration of ESBL-negative E. coli was easily decreased by photodynamic therapy; however, after a two-hour incubation period, the number of E. coli ESBL + colonies increased from 124 percent to 294 percent. Conclusion With the duration of the incubation period, the number of non-ESBL-producing K. Pneumonia increased. Even with longer incubation times, the number of K. Pneumonia ESBL + colonies decreased, contrary to expectations. The findings show that the two bacterial species differed in terms of cytotoxicity, interaction with urothelial cells, and photodynamic therapy response.
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Affiliation(s)
- Faisal Al-Sarraj
- Department of Biological Sciences, Faculty of Science, P.O. Box 80203, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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Zou H, Wang F, Zhou JJ, Liu X, He Q, Wang C, Zheng YW, Wen Y, Xiong L. Application of photodynamic therapy for liver malignancies. J Gastrointest Oncol 2020; 11:431-442. [PMID: 32399283 PMCID: PMC7212095 DOI: 10.21037/jgo.2020.02.10] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 02/14/2020] [Indexed: 12/11/2022] Open
Abstract
Liver malignancies include primary and metastatic tumors. Limited progress has been achieved in improving the survival rate of patients with advanced stage liver cancer and who are unsuitable for surgery. Apart from surgery, chemoradiotherapy, trans-arterial chemoembolization and radiofrequency ablation, a novel therapeutic modality is needed for the clinical treatment of liver cancer. Photodynamic therapy (PDT) is a novel strategy for treating patients with advanced cancers; it uses a light-triggered cytotoxic photosensitizer and a laser light. PDT provides patients with a potential treatment approach with minimal invasion and low toxicity, that is, the whole course of treatment is painless, harmless, and repeatable. Therefore, PDT has been considered an effective palliative treatment for advanced liver cancers. To date, PDT has been used to treat hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma and liver metastases. Clinical outcomes reveal that PDT can be considered a promising treatment modality for all liver cancers to improve the quality and quantity of life of patients. Despite the advances achieved with this approach, several challenges still impede the application of PDT to liver malignancies. In this review, we focus on the recent advancements and discuss the future prospects of PDT in treating liver malignancies.
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Affiliation(s)
- Heng Zou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Fusheng Wang
- Department of General Surgery, Fuyang People’s Hospital, Fuyang 236000, China
| | - Jiang-Jiao Zhou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Xi Liu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Qing He
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Cong Wang
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Yan-Wen Zheng
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Yu Wen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Li Xiong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
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de Freitas CF, Kimura E, Rubira AF, Muniz EC. Curcumin and silver nanoparticles carried out from polysaccharide-based hydrogels improved the photodynamic properties of curcumin through metal-enhanced singlet oxygen effect. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 112:110853. [PMID: 32409030 DOI: 10.1016/j.msec.2020.110853] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 02/10/2020] [Accepted: 03/13/2020] [Indexed: 01/23/2023]
Abstract
Colorectal cancer (CRC) has a high incidence and resistance to conventional treatments. Curcumin (CUR) is a promising natural product in the treatment of CRC with excellent in vitro results. However, its low bioavailability is a limiting factor in clinical applications. To overcome, CUR was incorporated into hydrogels constituted by chitosan (CHT) and chondroitin sulfate (CS), natural biopolymers, capable of controlled release. Hydrogels were synthesized in ionic liquids (ILs, [Hmim][HSO4]) improving the solubility of CHT and the hydrogel properties. Furthermore, CUR was combined with silver nanoparticles (AgNPs) and visible light by Photodynamic Therapy (PDT), which, through the MEO effect (Metal-Enhanced Singlet Oxygen), leads to cell death. It is highlighted the green synthesis of AgNPs using an ultrasound bath. The CHT/CS hydrogels loaded with CUR/AgNPs were properly characterized. Cellular assays showed that the hydrogels (CHT/CS) were not cytotoxic to healthy tissues. However, PDT selective illumination led to inhibition of Caco-2 human colon cancer cells by the CHT/CS/CUR-AgNPs (CC50 = 91.5 μg mL-1 of hydrogel). The cellular uptake assays showed, in addition to the therapeutic action, that the CUR can works as a diagnostic fluorescence probe (theranostic system). Finally, we highlight our commitment to work with reagents, solvents, and methodologies aiming at the principles of green chemistry.
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Affiliation(s)
- Camila Fabiano de Freitas
- Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil
| | - Elza Kimura
- Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil
| | - Adley Forti Rubira
- Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil
| | - Edvani Curti Muniz
- Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil; Department of Material Science, Federal University of Technology - Paraná, Estr. dos Pioneiros, 3131, CEP 86036-370, Jardim Morumbi, Londrina, Paraná, Brazil; Department of Chemistry, Federal University of Piauí, Campus Petronio Portella, Ininga, Teresina CEP 64049-550, Piauí, Brazil.
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10
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Gao Y, Zheng QC, Xu S, Yuan Y, Cheng X, Jiang S, Kenry, Yu Q, Song Z, Liu B, Li M. Theranostic Nanodots with Aggregation-Induced Emission Characteristic for Targeted and Image-Guided Photodynamic Therapy of Hepatocellular Carcinoma. Theranostics 2019; 9:1264-1279. [PMID: 30867829 PMCID: PMC6401505 DOI: 10.7150/thno.29101] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 11/16/2018] [Indexed: 12/21/2022] Open
Abstract
Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin ανβ3-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS. Methods: The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both in vitro and in vivo. The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining. Results: The obtained nanodots show bright red fluorescence and highly effective 1O2 generation in aggregate state. Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity. Conclusion: Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.
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Affiliation(s)
- Yang Gao
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Qi Chang Zheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shidang Xu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585
| | - Youyong Yuan
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585
| | - Xiang Cheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shuai Jiang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Kenry
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585
| | - Qihong Yu
- 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
| | - Bin Liu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China
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11
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Hamdan IM, Tekko IA, Matchett KB, Arnaut LG, Silva CS, McCarthy HO, Donnelly RF. Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays. J Pharm Sci 2018; 107:2439-2450. [DOI: 10.1016/j.xphs.2018.05.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 05/12/2018] [Accepted: 05/22/2018] [Indexed: 12/01/2022]
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12
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Hentzen JE, de Jongh SJ, Hemmer PH, van der Plas WY, van Dam GM, Kruijff S. Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: A narrative review. J Surg Oncol 2018; 118:332-343. [PMID: 29938400 PMCID: PMC6174973 DOI: 10.1002/jso.25106] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 04/16/2018] [Accepted: 04/22/2018] [Indexed: 12/14/2022]
Abstract
Patients with peritoneal carcinomatosis (PC) from colorectal origin may undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a curative approach. One major prognostic factor that affects survival is completeness of cytoreduction. Molecular Fluorescence Guided Surgery (MFGS) is a novel intraoperative imaging technique that may improve tumor identification in the future, potentially preventing over- and under-treatment in these patients. This narrative review outlines a chronological overview of MFGS development in patients with PC of colorectal origin.
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Affiliation(s)
- Judith E.K.R. Hentzen
- Department of Surgery, Division of Surgical Oncology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands
| | - Steven J. de Jongh
- Department of Gastroenterology and Hepatology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Patrick H.J. Hemmer
- Department of Surgery, Division of Surgical Oncology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands
| | - Willemijn Y. van der Plas
- Department of Surgery, Division of Surgical Oncology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands
| | - Gooitzen M. van Dam
- Department of Surgery, Division of Surgical Oncology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands
- Department of Nuclear Medicine and Molecular Imaging and Intensive Care, University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Schelto Kruijff
- Department of Surgery, Division of Surgical Oncology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands
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13
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Ou-Yang GQ, Pan GD, Wu YR, Xu HL. Orthotopic mouse models of colorectal cancer liver metastases. Shijie Huaren Xiaohua Zazhi 2018; 26:512-517. [DOI: 10.11569/wcjd.v26.i8.512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a malignancy with high incidence and mortality, and its high mortality rate is mainly attributed to metastases, with liver metastasis being the main cause of death. Appropriate animal models can provide a basis for studying the metastatic mechanism of colorectal cancer and assessing pre-clinical therapeutic effects. Orthotopic transplantation models that simulate colorectal cancer with liver metastases can better reflect the characteristic of liver metastasis in colorectal cancer. In this article, we review orthotopic transplantation models of liver metastases of colorectal cancer.
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Gao H, Shi L, Yin H, Wang H, Shen J, Wang C, Niu Q, Li Y, Li W, Dong M, Lu Y. Evaluation of the effect of photodynamic therapy with hematoporphyrin monomethyl ether on VX2 tumors implanted in the rectal submucosa of rabbits. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2016; 163:162-9. [DOI: 10.1016/j.jphotobiol.2016.08.038] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Revised: 08/19/2016] [Accepted: 08/23/2016] [Indexed: 12/11/2022]
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Mazzone G, Alberto ME, De Simone BC, Marino T, Russo N. Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations. Molecules 2016; 21:288. [PMID: 26938516 PMCID: PMC6273748 DOI: 10.3390/molecules21030288] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Revised: 02/19/2016] [Accepted: 02/24/2016] [Indexed: 01/10/2023] Open
Abstract
The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600-800 nm). The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin (Foscan©) already used in the photodynamic therapy (PDT) protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents.
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Affiliation(s)
- Gloria Mazzone
- Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, I-87036 Arcavacata di Rende, Italy.
| | - Marta E Alberto
- Chimie ParisTech, CNRS, Institut de Recherche de Chimie Paris (IRCP), PSL Research University, F-75005 Paris, France.
| | - Bruna C De Simone
- Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, I-87036 Arcavacata di Rende, Italy.
| | - Tiziana Marino
- Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, I-87036 Arcavacata di Rende, Italy.
| | - Nino Russo
- Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, I-87036 Arcavacata di Rende, Italy.
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Zhang LJ, O'Shea D, Zhang CY, Yan YJ, Wang L, Chen ZL. Evaluation of a bacteriochlorin-based photosensitizer's anti-tumor effect in vitro and in vivo. J Cancer Res Clin Oncol 2015; 141:1921-30. [PMID: 25804838 DOI: 10.1007/s00432-015-1960-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Accepted: 03/17/2015] [Indexed: 01/10/2023]
Abstract
PURPOSE Bacteriochlorin derivatives are promising photosensitive agents for photodynamic therapy (PDT) of tumors. In the current study, the photodynamic activity of a novel bacteriochlorin derivative, cis-2, 3, 12, 13-tetracarboxymethyl-5, 10, 15, 20-tetraphenyl bacteriochlorin (TCTB), was evaluated both in vitro and in vivo. METHODS Physicochemical characteristics of the novel photosensitizer were measured. The efficiency of TCTB-PDT in vitro was analyzed by MTT assay, clonogenic assay and in situ trypan blue exclusion test. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The accumulation of TCTB in human malignant tumor cells was measured by fluorescence spectrometer, and the pathway of cell death was analyzed by flow cytometry. S180 tumor model was used to evaluate the anti-tumor effects of TCTB-PDT. And histopathological study was also used to confirm the anti-tumor effect. RESULTS TCTB shows a singlet oxygen quantum yield of 0.56 and displays a characteristic long wavelength absorption peak at 732 nm. The accumulation of TCTB increased in time-dependent manner, and it was found in cytoplasm and nuclear membranes. In vitro PDT using TCTB and Nd:YAG laser showed drug concentration-, laser dose-dependent cytotoxicity to human esophageal cancer Eca-109 cells. In mice bearing osteosarcoma S180 tumors, the combined use of 10 mg/kg TCTB and 120 J/cm(2) showed superior anti-tumor activity. Histology examination of tumor tissues revealed that PDT using TCTB and the Nd:YAG laser induced tumor cells shrunken and necrotic. CONCLUSION In in vitro and in vivo studies, we found that TCTB has excellent anti-tumor effect. It suggests that TCTB is a potential photosensitizer of PDT for cancer.
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Affiliation(s)
- Li-Jun Zhang
- Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People's Republic of China
| | - Donal O'Shea
- Center for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland
| | - Chun-Ye Zhang
- Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People's Republic of China
| | - Yi-Jia Yan
- Shanghai Xianhui Pharmaceutical Co. Ltd, Shanghai, 200433, People's Republic of China
| | - Li Wang
- Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People's Republic of China
| | - Zhi-Long Chen
- Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People's Republic of China.
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Photodynamic therapy in colorectal cancer treatment: the state of the art in clinical trials. Photodiagnosis Photodyn Ther 2015; 12:545-53. [PMID: 25930668 DOI: 10.1016/j.pdpdt.2015.04.004] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 04/10/2015] [Indexed: 12/29/2022]
Abstract
BACKGROUND Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer. This review aims to give a general overview of the PDT application to colorectal cancer in the field of clinical trials to emphasize its curative, and insufficiently exploited potential. MATERIALS AND METHODS Literature on PDT for colorectal cancer with the following medical subject headings search terms: colorectal cancer, photodynamic therapy, clinical trials was reviewed. The articles were selected by their relevance to the topic. RESULTS There are many positive and promising trial results from I to II/III phase for the use of PDT in colorectal cancer both in less advanced tumors as well as in the palliative therapy of advanced lesions. CONCLUDING REMARKS PDT seems to be a safe and a feasible treatment option for colorectal cancer. Theoretical assumptions confirmed by many results of preclinical studies taking into consideration an increasing number of analyzed clinical trials, should lead to the development of optimized standards by using PDT in colorectal cancer treatment.
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Riyad YM, Naumov S, Schastak S, Griebel J, Kahnt A, Häupl T, Neuhaus J, Abel B, Hermann R. Chemical Modification of a Tetrapyrrole-Type Photosensitizer: Tuning Application and Photochemical Action beyond the Singlet Oxygen Channel. J Phys Chem B 2014; 118:11646-58. [DOI: 10.1021/jp507270k] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Yasser M. Riyad
- Wilhelm-Ostwald-Institute
for Physical and Theoretical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Permoserstrasse 15, 04318 Leipzig, Germany
- Chemistry
Department, Faculty of Science, Al-Azhar University, Nasr City, 11884, Cairo, Egypt
| | - Sergej Naumov
- Chemical
Department, Leibniz Institute of Surface Modification, Permoserstrasse
15, 04318 Leipzig, Germany
| | - Stanislaw Schastak
- Department
of Ophthalmology, Faculty of Medicine, Univeristy of Leipzig, Liebigstrasse
10-14, 04103 Leipzig, Germany
- Laser-Medical Center e.V., Liebigstrasse
10-14, 04103 Leipzig, Germany
| | - Jan Griebel
- Wilhelm-Ostwald-Institute
for Physical and Theoretical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Permoserstrasse 15, 04318 Leipzig, Germany
| | - Axel Kahnt
- Department
of Chemistry and Pharmacy and Interdisciplinary Center for Molecular
Materials, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen, Germany
| | - Tilmann Häupl
- Wilhelm-Ostwald-Institute
for Physical and Theoretical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Permoserstrasse 15, 04318 Leipzig, Germany
| | - Jochen Neuhaus
- Department
of Urology, University of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Bernd Abel
- Wilhelm-Ostwald-Institute
for Physical and Theoretical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Permoserstrasse 15, 04318 Leipzig, Germany
- Chemical
Department, Leibniz Institute of Surface Modification, Permoserstrasse
15, 04318 Leipzig, Germany
| | - Ralf Hermann
- Wilhelm-Ostwald-Institute
for Physical and Theoretical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Permoserstrasse 15, 04318 Leipzig, Germany
- Laser-Medical Center e.V., Liebigstrasse
10-14, 04103 Leipzig, Germany
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Krzykawska-Serda M, Dąbrowski JM, Arnaut LG, Szczygieł M, Urbańska K, Stochel G, Elas M. The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy. Free Radic Biol Med 2014; 73:239-51. [PMID: 24835769 DOI: 10.1016/j.freeradbiomed.2014.05.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Revised: 05/02/2014] [Accepted: 05/02/2014] [Indexed: 12/22/2022]
Abstract
Blood flow and pO2 changes after vascular-targeted photodynamic therapy (V-PDT) or cellular-targeted PDT (C-PDT) using 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl) bacteriochlorin (F2BMet) as photosensitizer were investigated in DBA/2 mice with S91 Cloudman mouse melanoma, and correlated with long-term tumor responses. F2BMet generates both singlet oxygen and hydroxyl radicals under near-infrared radiation, which consume oxygen. Partial oxygen pressure was lowered in PDT-treated tumors and this was ascribed both to oxygen consumption during PDT and to fluctuations in oxygen transport after PDT. Similarly, microcirculatory blood flow changed as a result of the disruption of blood vessels by the treatment. A novel noninvasive approach combining electron paramagnetic resonance oximetry and laser Doppler blood perfusion measurements allowed longitudinal monitoring of hypoxia and vascular function changes in the same animals, after PDT. C-PDT induced parallel changes in tumor pO2 and blood flow, i.e., an initial decrease immediately after treatment, followed by a slow increase. In contrast, V-PDT led to a strong and persistent depletion of pO2, although the microcirculatory blood flow increased. Strong hypoxia after V-PDT led to a slight increase in VEGF level 24h after treatment. C-PDT caused a ca. 5-day delay in tumor growth, whereas V-PDT was much more efficient and led to tumor growth inhibition in 90% of animals. The tumors of 44% of mice treated with V-PDT regressed completely and did not reappear for over 1 year. In conclusion, mild and transient hypoxia after C-PDT led to intense pO2 compensatory effects and modest tumor inhibition, but strong and persistent local hypoxia after V-PDT caused tumor growth inhibition.
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Affiliation(s)
- Martyna Krzykawska-Serda
- Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
| | | | - Luis G Arnaut
- Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal; Luzitin SA, 3045-016 Coimbra, Portugal.
| | - Małgorzata Szczygieł
- Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
| | - Krystyna Urbańska
- Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
| | - Grażyna Stochel
- Faculty of Chemistry, Jagiellonian University, 30-060 Krakow, Poland
| | - Martyna Elas
- Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.
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20
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Shishkova N, Kuznetsova O, Berezov T. Photodynamic Therapy in Gastroenterology. J Gastrointest Cancer 2013; 44:251-9. [DOI: 10.1007/s12029-013-9496-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Machado AHA, Soares PC, Da Silva NS, Moraes KC. Cellular and molecular studies of the initial process of the photodynamic therapy in HEp-2 cells using LED light source and two different photosensitizers. Cell Biol Int 2013; 33:785-95. [DOI: 10.1016/j.cellbi.2009.04.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2008] [Revised: 03/12/2009] [Accepted: 04/14/2009] [Indexed: 01/22/2023]
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22
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Yuan KH, Gao JH, Huang Z. Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks. Photodiagnosis Photodyn Ther 2012. [DOI: 10.1016/j.pdpdt.2012.03.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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23
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Dąbrowski JM, Arnaut LG, Pereira MM, Urbańska K, Simões S, Stochel G, Cortes L. Combined effects of singlet oxygen and hydroxyl radical in photodynamic therapy with photostable bacteriochlorins: evidence from intracellular fluorescence and increased photodynamic efficacy in vitro. Free Radic Biol Med 2012; 52:1188-200. [PMID: 22285766 DOI: 10.1016/j.freeradbiomed.2011.12.027] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Revised: 12/22/2011] [Accepted: 12/28/2011] [Indexed: 01/08/2023]
Abstract
Sulfonamides of halogenated bacteriochlorins bearing Cl or F substituents in the ortho positions of the phenyl rings have adequate properties for photodynamic therapy, including strong absorption in the near-infrared (λ(max) ≈ 750 nm, ε ≈ 10(5) M(-1) cm(-1)), controlled photodecomposition, large cellular uptake, intracellular localization in the endoplasmic reticulum, low cytotoxicity, and high phototoxicity against A549 and S91 cells. The roles of type I and type II photochemical processes are assessed by singlet oxygen luminescence and intracellular hydroxyl radical detection. Phototoxicity of halogenated sulfonamide bacteriochlorins does not correlate with singlet oxygen quantum yields and must be mediated both by electron transfer (superoxide ion, hydroxyl radicals) and by energy transfer (singlet oxygen). The photodynamic efficacy is enhanced when cellular death is induced by both singlet oxygen and hydroxyl radicals.
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24
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Dąbrowski JM, Krzykawska M, Arnaut LG, Pereira MM, Monteiro CJP, Simões S, Urbańska K, Stochel G. Tissue Uptake Study and Photodynamic Therapy of Melanoma-Bearing Mice with a Nontoxic, Effective Chlorin. ChemMedChem 2011; 6:1715-26. [DOI: 10.1002/cmdc.201100186] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Revised: 06/05/2011] [Indexed: 02/06/2023]
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25
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Susan M, Baldea I, Senila S, Macovei V, Dreve S, Ion RM, Cosgarea R. Photodamaging effects of porphyrins and chitosan on primary human keratinocytes and carcinoma cell cultures. Int J Dermatol 2011; 50:280-6. [PMID: 21342160 DOI: 10.1111/j.1365-4632.2010.04700.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Photodynamic therapy (PDT) is a non-surgical method for treating non-melanoma skin cancer and precancerous lesions which involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in the destruction of the latter. The present study evaluates the effect of PDT on primary normal and basal cell carcinoma cultures in vitro. METHODS Primary human keratinocytes and carcinoma cell cultures were exposed to various concentrations of 5,10,15,20-tetra-(para-methoxyphenyl) porphyrin (TMP) and its zinc compound (Zn-TMP) for 24 hours, with or without chitosan, and then irradiated using a PDT lamp (630 nm, 6 J/cm(2)). The effects of PDT were assessed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and an immunocytochemical method with Annexin V-FITC for detecting apoptosis. RESULTS Both tested substances, TMP and Zn-TMP, had a phototoxic effect on primary human carcinoma cell cultures in concentrations of 1-100 μg/ml, which positively correlated with the concentration of the photosensitizer. There was no phototoxic effect on primary keratinocytes, probably because of the preferential accumulation of photosensitizing substances in tumoral cells. Administration of chitosan in association with photosensitizing substances increased cell viability compared with photosensitizers alone, exerting a cytoprotective effect. CONCLUSIONS The study demonstrates that the photodynamic activity of TMP and its metalloporphyrin derivative is limited to primary human carcinoma cells and suggests that these porphyrins could be efficiently used in PDT in vivo.
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Affiliation(s)
- Mirela Susan
- Department of Dermatology, University of Medicine and Pharmacy, Cluj-Napoca, Romania
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26
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Krayer M, Yang E, Diers JR, Bocian DF, Holten D, Lindsey JS. De novo synthesis and photophysical characterization of annulated bacteriochlorins. Mimicking and extending the properties of bacteriochlorophylls. NEW J CHEM 2011. [DOI: 10.1039/c0nj00771d] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Silva EFF, Serpa C, Dabrowski JM, Monteiro CJP, Formosinho SJ, Stochel G, Urbanska K, Simões S, Pereira MM, Arnaut LG. Mechanisms of singlet-oxygen and superoxide-ion generation by porphyrins and bacteriochlorins and their implications in photodynamic therapy. Chemistry 2010; 16:9273-86. [PMID: 20572171 DOI: 10.1002/chem.201000111] [Citation(s) in RCA: 134] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction.
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Affiliation(s)
- Elsa F F Silva
- Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal
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Stable synthetic cationic bacteriochlorins as selective antimicrobial photosensitizers. Antimicrob Agents Chemother 2010; 54:3834-41. [PMID: 20625146 DOI: 10.1128/aac.00125-10] [Citation(s) in RCA: 106] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Photodynamic inactivation is a rapidly developing antimicrobial treatment that employs a nontoxic photoactivatable dye or photosensitizer in combination with harmless visible light to generate reactive oxygen species that are toxic to cells. Tetrapyrroles (e.g., porphyrins, chlorins, bacteriochlorins) are a class of photosensitizers that exhibit promising characteristics to serve as broad-spectrum antimicrobials. In order to bind to and efficiently penetrate into all classes of microbial cells, tetrapyrroles should have structures that contain (i) one or more cationic charge(s) or (ii) a basic group. In this report, we investigate the use of new stable synthetic bacteriochlorins that have a strong absorption band in the range 720 to 740 nm, which is in the near-infrared spectral region. Four bacteriochlorins with 2, 4, or 6 quaternized ammonium groups or 2 basic amine groups were compared for light-mediated killing against a gram-positive bacterium (Staphylococcus aureus), a gram-negative bacterium (Escherichia coli), and a dimorphic fungal yeast (Candida albicans). Selectivity was assessed by determining phototoxicity against human HeLa cancer cells under the same conditions. All four compounds were highly active (6 logs of killing at 1 microM or less) against S. aureus and showed selectivity for bacteria over human cells. Increasing the cationic charge increased activity against E. coli. Only the compound with basic groups was highly active against C. albicans. Supporting photochemical and theoretical characterization studies indicate that (i) the four bacteriochlorins have comparable photophysical features in homogeneous solution and (ii) the anticipated redox characteristics do not correlate with cell-killing ability. These results support the interpretation that the disparate biological activities observed stem from cellular binding and localization effects rather than intrinsic electronic properties. These findings further establish cationic bacteriochlorins as extremely active and selective near-infrared activated antimicrobial photosensitizers, and the results provide fundamental information on structure-activity relationships for antimicrobial photosensitizers.
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Small W, Singhal P, Wilson TS, Maitland DJ. Biomedical applications of thermally activated shape memory polymers. JOURNAL OF MATERIALS CHEMISTRY 2010; 20:3356-3366. [PMID: 21258605 PMCID: PMC3023912 DOI: 10.1039/b923717h] [Citation(s) in RCA: 213] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Shape memory polymers (SMPs) are smart materials that can remember a primary shape and can return to this primary shape from a deformed secondary shape when given an appropriate stimulus. This property allows them to be delivered in a compact form via minimally invasive surgeries in humans, and deployed to achieve complex final shapes. Here we review the various biomedical applications of SMPs and the challenges they face with respect to actuation and biocompatibility. While shape memory behavior has been demonstrated with heat, light and chemical environment, here we focus our discussion on thermally stimulated SMPs.
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Affiliation(s)
- Ward Small
- Lawrence Livermore National Laboratory, Livermore, California, 94550, USA
| | - Pooja Singhal
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, 77843, USA
| | - Thomas S. Wilson
- Lawrence Livermore National Laboratory, Livermore, California, 94550, USA
| | - Duncan J. Maitland
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, 77843, USA
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Zhai B, Xu AM, Li XY, Liu S, Chen Y, Wu MC. Risk factors of rapid and extensive intrahepatic neoplastic progression after radiofrequency ablation in hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2008; 16:1815-1819. [DOI: 10.11569/wcjd.v16.i16.1815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the mechanism and influencing factors of rapid and extensive intrahepatic neoplastic progression after radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients.
METHODS: A total of 926 consecutive HCC patients admitted to RFA between January 1999 and June 2006 were enrolled. In all cases RFA was performed with percutaneous approach under ultrasound guidance. Treatment efficacy (necrosis and recurrence) was assessed using dual phase computed tomography (CT) or MRI and alpha-fetoprotein (AFP) level within 45 days after RFA treatment. Ten potential variables for rapid and extensive intrahepatic neoplastic progression were analyzed, including liver function Child-Pugh classification, the number of tumor, size, location, growth pattern, AFP value, tumor differentiation, portal vein cancerous thrombosis, the type of RF treatment system (or electrode-type) and transarterial chemoembolization (TACE).
RESULTS: Complete follow-up data were obtained from 874 cases of patients (94.4%). In 54 patients, although complete local necrosis was achieved, we observed rapid intrahepatic neoplastic progression 30-45 d after treatment. Risk factors analysis by Logistic regression suggested risk factors for rapid and extensive intrahepatic neoplastic progression of HCC after RFA were tumor type, portal vein cancerous thrombosis, tumor cite and TACE treatment (OR = 2.647, P < 0.001; OR = 1.341, P < 0.001; OR = 0.197, P = 0.006; OR = 1.512, P = 0.042, respectively).
CONCLUSION: RFA is an effective treatment for HCC. Tumor near portal branches, infiltrative growth, vessel invasion of portal branches and TACE treatment are risk factors for rapid neoplastic progression after RFA. TACE treatment is a better choice for those patients.
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Small W, Buckley PR, Wilson TS, Loge JM, Maitland KD, Maitland DJ. Fabrication and characterization of cylindrical light diffusers comprised of shape memory polymer. JOURNAL OF BIOMEDICAL OPTICS 2008; 13:024018. [PMID: 18465981 PMCID: PMC2637550 DOI: 10.1117/1.2904952] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
We developed a technique for constructing light diffusing devices comprised of a flexible shape memory polymer (SMP) cylindrical diffuser attached to the tip of an optical fiber. The devices are fabricated by casting an SMP rod over the cleaved tip of an optical fiber and media blasting the SMP rod to create a light diffusing surface. The axial and polar emission profiles and circumferential (azimuthal) uniformity are characterized for various blasting pressures, nozzle-to-sample distances, and nozzle translation speeds. The diffusers are generally strongly forward-directed and consistently withstand over 8 W of incident IR laser light without suffering damage when immersed in water. These devices are suitable for various endoluminal and interstitial biomedical applications.
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Affiliation(s)
- Ward Small
- Lawrence Livermore National Laboratory, 7000 East Avenue, L-211, Livermore, California 94550, USA.
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Abstract
This paper reviews the photodynamic therapy for gastrointestinal tumors and its mechanisms, and describes the authors' experience with it. It is feasible and reasonable to use photodynamic therapy for gastrointestinal tumors. It is not in contradiction with PDT and traditional surgical treatment, chemotherapy, radiation and immune therapy, etc. The main mechanisms of photodynamic therapy for gastrointestinal tumors are to damage tumor microvasculature, induce cancer cell apoptosis, injure cancer cell membrane, and trigger immune reactions.
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Abstract
Photodynamic therapy (PDT) combines a drug (a photosensitiser or photosensitising agent) with a specific type of light to kill cancer cells. It is a minimally invasive treatment, with great potential in malignant disease and premalignant conditions. Following the administration of the photosensitiser, light of the appropriate wavelength is directed onto the abnormal tissue where the drug has preferentially accumulated. Upon light activation, the photosensitiser transfers its excess energy to molecular oxygen to produce an excited state (i.e., the highly reactive singlet oxygen) that causes oxidative damage at the site of its generation. The energy transfer occurs either directly to oxygen or through an indirect mechanism that requires the formation of intermediate radical species. Many photosensitisers have been developed, but only a few have been approved for therapy in humans. Basic research in model systems (animals, cell lines) has unravelled some fundamental cellular processes involved in the cell response to PDT. The exploitation of relevant molecular observations, the discovery and introduction of new sensitisers, the progress in the light delivery systems and light dosimetry are all concurring to the increase of PDT therapeutic efficacy. However, this field has not yet reached maturity. This review briefly analyses the relevant properties of most photosensitisers and their field of application. Special attention is dedicated to the effects observed in model cancer systems; speculation and suggestions of possible future research directions are also offered.
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Affiliation(s)
- Giuseppe Palumbo
- University Federico II Naples, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano and IEOS/CNR, Napoli, Via S. Pansini, 5 80131-Napoli, Italy.
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Yow CMN, Wong CK, Huang Z, Ho RJ. Study of the efficacy and mechanism of ALA-mediated photodynamic therapy on human hepatocellular carcinoma cell. Liver Int 2007; 27:201-8. [PMID: 17311614 DOI: 10.1111/j.1478-3231.2006.01412.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
OBJECTIVES To examine the efficacy and mechanism of delta- or 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on a human hepatocellular carcinoma cell line. MATERIALS AND METHODS The optimal uptake of photosensitizer ALA in HepG2 (p53 wild) cells was investigated by means of spectrometric measurement. Cell viability was determined by trypan blue exclusion assay. Morphological apoptotic changes in HepG2 cells before and after ALA-mediated PDT were determined by microscopic examination. Detection of apoptotic bodies was examined by DAPI staining. The changes in p53 expression were revealed by the immunostaining method. RESULTS ALA/protoporphyrin IX (PpIX) was mainly located in the cytoplasm of HepG2 cells. The maximal cellular uptake occurred after 18 h in vitro incubation. The photocytotoxic assay showed that ALA PDT induced 80% killing at 2 mM drug dose and 2 J/cm2 light intensity. Up to 70% of cells showed membrane blebbing and positive DAPI staining, indicating that ALA-PDT-mediated cell death was predominantly via apoptosis. In addition, p53 was upregulated after treatment, implying that p53 might evoke apoptotic cell death. CONCLUSIONS HepG2 cell line is sensitive to ALA-mediated PDT. ALA-PDT induces apoptosis in the HepG2 cell line that may be mediated by a p53-dependent pathway.
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Affiliation(s)
- C M N Yow
- Department of Health Technology Informatics, Hong Kong Polytechnic University, Hung Hom, HKSAR, China.
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Waldman SA, Fortina P, Surrey S, Hyslop T, Kricka LJ, Graves DJ. Opportunities for near-infrared thermal ablation of colorectal metastases by guanylyl cyclase C-targeted gold nanoshells. Future Oncol 2007; 2:705-16. [PMID: 17155897 DOI: 10.2217/14796694.2.6.705] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Colorectal cancer is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. While surgery remains the mainstay of therapy, approximately 50% of patients who undergo resection develop parenchymal metastatic disease. Unfortunately, current therapeutic regimens offer little improvement to the survival of patients with parenchymal metastases in the liver and lung. In that context, there is a significant unrealized opportunity at the intersection of engineering and biology for the development of novel targeted therapeutic approaches to colorectal cancer metastases. This opportunity exploits the discovery that an intestinal receptor, guanylyl cyclase C, which mediates diarrhea induced by bacterial heat-stable enterotoxins (STs), is over-expressed by metastatic colorectal tumors only. Moreover, it leverages recent advances in the fabrication of metal nanoshells with defined thicknesses absorb near-infrared (NIR) light, resulting in resonance and transfer of thermal energies of more than 40 degrees C. Thus, the conjugation of ST to gold nanoshells, which can undergo resonance excitation by NIR light and emit heat, represents a previously unrecognized approach for the targeted therapy of parenchymal colorectal cancer metastases, specifically to the liver and lung. This article discusses the potential of ST-targeted nanoshells for NIR thermal ablation of metastatic colorectal tumors and highlights the significant challenges and solutions linked to the translation of this emerging technology to patient care.
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Affiliation(s)
- Scott A Waldman
- Thomas Jefferson University, Jefferson Medical College, Department of Pharmacology & Experimental Therapeutics, Philadelphia, PA 19107, USA.
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Rendon A, Weersink R, Lilge L. Towards conformal light delivery using tailored cylindrical diffusers: attainable light dose distributions. Phys Med Biol 2006; 51:5967-75. [PMID: 17110763 DOI: 10.1088/0031-9155/51/23/001] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Interstitial light delivery for therapeutic applications requires the use of fibre-based light diffusers. Such diffusers are presently manufactured to emit with a flat longitudinal power profile. Recently, diffusers with tailored longitudinal emission profiles have become available opening an avenue to improve conformal light delivery. This paper explores the ability of tailored diffusers to improve light dose confinement to the target volume. A formalism to calculate the light dose from an arbitrary source distribution is presented based on the convolution with an appropriate point source function. By choosing a source distribution corresponding to a cylindrical diffuser emitting with a sinusoidal profile, the set of attainable light dose distributions is characterized via a relationship between the diffuser's spatial frequency, the radial distance and the amplitude of the isodose contour.
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Affiliation(s)
- Augusto Rendon
- Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9, Canada
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Chin WWL, Lau WKO, Heng PWS, Bhuvaneswari R, Olivo M. Fluorescence imaging and phototoxicity effects of new formulation of chlorin e6–polyvinylpyrrolidone. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2006; 84:103-10. [PMID: 16542848 DOI: 10.1016/j.jphotobiol.2006.02.002] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2005] [Accepted: 02/02/2006] [Indexed: 11/26/2022]
Abstract
Evaluations of the efficiency of a new formulation of chlorin consisting of a complex of trisodium salt chlorin e6 (Ce6) and polyvinylpyrrolidone (PVP) in photodynamic therapy (PDT) and fluorescence diagnosis was performed on poorly differentiated human bladder carcinoma murine model with the following specific aims: (i) to qualitatively evaluate the fluorescence accumulation in human bladder tumor, (ii) to determine fluorescence distribution of Ce6-PVP using the tissue extraction technique and fluorescence imaging technique, (iii) to compare the fluorescence distribution of Ce6, Ce6-PVP and Photofrin in skin of nude mice, and (iv) to investigate phototoxicity caused by different parameters (drug-light interval, drug dose, irradiation fluence rate and total light fluence) in PDT. The fluorescence of the Ce6-PVP formulation was determined either by fluorescence imaging measurements or by chemical extraction from the tissues displaying similar trends of distribution. Our results demonstrated that the Ce6-PVP formulation possesses less in vivo phototoxic effect compared to Ce6 alone. The phototoxicity revealed a strong dependence on the drug and light dosimetry as well as on the drug-light interval. In PDT, the Ce6-PVP compound was most toxic at the 1h drug-light interval at 200J/cm(2), while Ce6 alone was most toxic at a light dose of more that 50J/cm(2) at the 1 and 3h drug-light interval. We also confirmed that Ce6-PVP has a faster clearance compared to Ce6 alone or Photofrin. This eliminates the need for long-term photosensitivity precautions. In conclusion, the Ce6-PVP formulation seems to be a promising photosensitizer for fluorescence imaging as well as for photodynamic treatment.
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Affiliation(s)
- William Wei Lim Chin
- Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore
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John Wiley & Sons, Ltd.. Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2006. [DOI: 10.1002/pds.1177] [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]
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