Stimulus‐Detonated Biomimetic “Nanobomb” with Controlled Release of HSP90 Inhibitor to Disrupt Mitochondrial Function for Synergistic Gas and Photothermal Therapy
Geng Yang, Ting Song, Hanxi Zhang, Mengyue Li, Xiaodan Wei, Wanyi Zhou, Chunhui Wu, Yiyao Liu, Hong Yang
Abstract
Abstract 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 H 2 O 2 ‐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 Mn 2+ 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.