Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer
The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluro...
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doaj-1bf4a28172eb410aad49a437275fb65e2020-11-25T00:07:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-04-011010.3389/fphar.2019.00369455564Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast CancerChan Feng0Donglei Zhu1Lv Chen2Yonglin Lu3Jie Liu4Na Yoon Kim5Shujing Liang6Xia Zhang7Yun Lin8Yabin Ma9Chunyan Dong10Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaDepartment of Chemical Engineering, Northeastern University, Boston, MA, United StatesCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaPharmacy Department, Shanghai East Hospital, Tongji University, Shanghai, ChinaCancer Center, Shanghai East Hospital, Tongji University, Shanghai, ChinaThe off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency.https://www.frontiersin.org/article/10.3389/fphar.2019.00369/fullchlorin e6redox sensitivediselenidephotodynamic therapycluster of differentiation 44targeted delivery |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chan Feng Donglei Zhu Lv Chen Yonglin Lu Jie Liu Na Yoon Kim Shujing Liang Xia Zhang Yun Lin Yabin Ma Chunyan Dong |
spellingShingle |
Chan Feng Donglei Zhu Lv Chen Yonglin Lu Jie Liu Na Yoon Kim Shujing Liang Xia Zhang Yun Lin Yabin Ma Chunyan Dong Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer Frontiers in Pharmacology chlorin e6 redox sensitive diselenide photodynamic therapy cluster of differentiation 44 targeted delivery |
author_facet |
Chan Feng Donglei Zhu Lv Chen Yonglin Lu Jie Liu Na Yoon Kim Shujing Liang Xia Zhang Yun Lin Yabin Ma Chunyan Dong |
author_sort |
Chan Feng |
title |
Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer |
title_short |
Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer |
title_full |
Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer |
title_fullStr |
Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer |
title_full_unstemmed |
Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer |
title_sort |
targeted delivery of chlorin e6 via redox sensitive diselenide-containing micelles for improved photodynamic therapy in cluster of differentiation 44-overexpressing breast cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-04-01 |
description |
The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency. |
topic |
chlorin e6 redox sensitive diselenide photodynamic therapy cluster of differentiation 44 targeted delivery |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00369/full |
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