Stimulus-Detonated Biomimetic "Nanobomb" with Controlled Release of HSP90 Inhibitor to Disrupt Mitochondrial Function for Synergistic Gas and Photothermal Therapy.

Photothermal therapy (PTT) is considered a promising treatment for tumors, however, the efficacy of which is restricted by the overexpression of heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) was designed for synergistic gas therapy and enhanced PTT. This nanoplatform was 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 gas. 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 was methodically appraised and validated both in vitro and in vivo. Taken together, this study afforded a prime paradigm for applying this strategy for enhanced cancer photothermal therapy via mitochondrial dysfunction. This article is protected by copyright. All rights reserved.