pH/GSH dual responsive nanosystem for nitric oxide generation enhanced type I photodynamic therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38292411.
- Also identified by DOI 10.1016/j.bioactmat.2023.12.023 and PMC identifier 10825229.
- Licence recorded as CC BY-NC-ND.
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Abstract
Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently of oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment (TME) to enhance type I PDT through glutathione (GSH) depletion. Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals (O<sub>2</sub><sup>-.</sup>) while minimizing their consumption. The diisopropyl group within PEG-IR820 serves a dual purpose: it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820, facilitating efficient O<sub>2</sub><sup>-.</sup> generation. Simultaneously, the release of JSK leads to GSH depletion, resulting in the generation of nitric oxide (NO). This, in turn, contributes to the formation of highly cytotoxic peroxynitrite (ONOO<sup>-.</sup>), thereby enhancing the therapeutic efficacy of these NPs. NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.