Abstract |
Currently, activatable photodynamic therapy ( PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was "double-locked" by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the "double-key", which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT- PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.
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Authors | YiCong Li, DanRong Hu, Meng Pan, Ying Qu, BingYang Chu, JinFeng Liao, XiaoHan Zhou, QingYa Liu, Shuang Cheng, Yu Chen, Quan Wei, ZhiYong Qian |
Journal | Biomaterials
(Biomaterials)
Vol. 288
Pg. 121700
(09 2022)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 36049897
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2022 Elsevier Ltd. All rights reserved. |
Chemical References |
- Chlorophyllides
- Photosensitizing Agents
- Porphyrins
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Topics |
- Animals
- Cell Line, Tumor
- Chlorophyllides
(therapeutic use)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Nanoparticles
(chemistry)
- Neoplasms
(drug therapy)
- Oxidation-Reduction
- Photochemotherapy
(methods)
- Photosensitizing Agents
(chemistry, therapeutic use)
- Phototherapy
- Porphyrins
(chemistry)
- Tumor Microenvironment
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