Application of tumor pH/hypoxia-responsive nanoparticles for combined photodynamic therapy and hypoxia-activated chemotherapy
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Published:2023-06-09
Issue:
Volume:11
Page:
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ISSN:2296-4185
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Container-title:Frontiers in Bioengineering and Biotechnology
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language:
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Short-container-title:Front. Bioeng. Biotechnol.
Author:
Zhang Zhang,Feng Jintang,Zhang Tianzhu,Gao An,Sun Chunyang
Abstract
Introduction: Cancer selectivity, including targeted internalization and accelerated drug release in tumor cells, remains a major challenge for designing novel stimuli-responsive nanocarriers to promote therapeutic efficacy. The hypoxic microenvironment created by photodynamic therapy (PDT) is believed to play a critical role in chemoresistance.Methods: We construct dual-responsive carriers (DANPCT) that encapsulate the photosensitizer chlorin e6 (Ce6) and hypoxia-activated prodrug tirapazamine (TPZ) to enable efficient PDT and PDT-boosted hypoxia-activated chemotherapy.Results and discussion: Due to TAT masking, DANPCT prolonged payload circulation in the bloodstream, and selective tumor cell uptake occurred via acidity-triggered TAT presentation. PDT was performed with a spatially controlled 660-nm laser to enable precise cell killing and exacerbate hypoxia. Hypoxia-responsive conversion of the hydrophobic NI moiety led to the disassembly of DANPCT, facilitating TPZ release. TPZ was reduced to cytotoxic radicals under hypoxic conditions, contributing to the chemotherapeutic cascade. This work offers a sophisticated strategy for programmed chemo-PDT.
Funder
National Natural Science Foundation of China
Tianjin Science and Technology Committee
Tianjin Municipal Health Commission
Wu Jieping Medical Foundation
Publisher
Frontiers Media SA
Subject
Biomedical Engineering,Histology,Bioengineering,Biotechnology