期刊
ADVANCED HEALTHCARE MATERIALS
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202300945
关键词
gas therapy; heat shock protein; magnetic imaging; mitochondrial dysfunction; photothermal therapy
Photothermal therapy (PTT) is a promising treatment for tumors, but it is limited by heat shock proteins (HSPs). In this study, a stimuli-responsive theranostic nanoplatform is designed for synergistic gas therapy and PTT. The nanoplatform combines photothermal effect, controlled drug release, and gas therapy to enhance PTT efficacy via mitochondrial dysfunction.
Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H2O2-rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn2+ enables T-1-weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.
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