Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy

Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen ((1)O(2))...

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Autores principales: Yuan, Jie, Peng, Rong, Su, Dongdong, Zhang, Xingxing, Zhao, Hepeng, Zhuang, Xiujuan, Chen, Mei, Zhang, Xiaobing, Yuan, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847693/
https://www.ncbi.nlm.nih.gov/pubmed/33537100
http://dx.doi.org/10.7150/thno.55014
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author Yuan, Jie
Peng, Rong
Su, Dongdong
Zhang, Xingxing
Zhao, Hepeng
Zhuang, Xiujuan
Chen, Mei
Zhang, Xiaobing
Yuan, Lin
author_facet Yuan, Jie
Peng, Rong
Su, Dongdong
Zhang, Xingxing
Zhao, Hepeng
Zhuang, Xiujuan
Chen, Mei
Zhang, Xiaobing
Yuan, Lin
author_sort Yuan, Jie
collection PubMed
description Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen ((1)O(2)), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of (1)O(2) on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs.
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spelling pubmed-78476932021-02-02 Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy Yuan, Jie Peng, Rong Su, Dongdong Zhang, Xingxing Zhao, Hepeng Zhuang, Xiujuan Chen, Mei Zhang, Xiaobing Yuan, Lin Theranostics Research Paper Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen ((1)O(2)), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of (1)O(2) on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs. Ivyspring International Publisher 2021-01-19 /pmc/articles/PMC7847693/ /pubmed/33537100 http://dx.doi.org/10.7150/thno.55014 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Yuan, Jie
Peng, Rong
Su, Dongdong
Zhang, Xingxing
Zhao, Hepeng
Zhuang, Xiujuan
Chen, Mei
Zhang, Xiaobing
Yuan, Lin
Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
title Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
title_full Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
title_fullStr Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
title_full_unstemmed Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
title_short Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
title_sort cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847693/
https://www.ncbi.nlm.nih.gov/pubmed/33537100
http://dx.doi.org/10.7150/thno.55014
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