AbstractDrug delivery systems (DDSs) capable of sequential multistage drug release are urgently needed for antibacterial applications. Herein, a molecular switch‐integrated, photo‐responsive nanoplatform is reported based on hollow mesoporous silica nanospheres (HMSN) loaded with silver nanoparticles (Ag NPs), vancomycin (Van), and hemin (HAVH) for bacteria elimination and abscess therapy. Upon near‐infrared (NIR) light irradiation, the molecular switch, hemin, can effuse from the mesopores of HMSN, triggering the release of pre‐loaded Ag+ and Van, which enables photothermal‐modulated drug release and synergistic photothermal‐chemo therapy (PTT‐CHT). The HAVH_NIR irreversibly disrupts the bacterial cell membrane, facilitating the penetration of Ag+ and Van. It is found that these compounds restrain the transcription and translation of ribosomes and lead to rapid bacterial death. Furthermore, hemin can effectively inhibit excessive inflammatory responses associated with the treatment, promoting accelerated wound healing in a murine abscess model. This work presents a new strategy for antibacterial drug delivery with high controllability and extendibility, which may benefit the development of smart multifunctional nanomedicine for diseases not limited to bacterial infections.

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