Hyaluronidase-responsive phototheranostic nanoagents for fluorescence imaging and photothermal/photodynamic therapy of methicillin-resistant Staphylococcus aureus infections.

Infectious diseases associated with antibiotic-resistant bacteria are ever-growing threats to public health. Effective treatment and detection methods of bacterial infections are in urgent demand. Herein, novel phototheranostic nanoagents (MoS2@HA-Ce6 nanosheets, MHC NSs) with hyaluronidase (HAase)-responsive fluorescence imaging (FLI) and photothermal/photodynamic therapy (PTT/PDT) functions were prepared. In this design, Ce6 is used as both a photosensitizer and a fluorescent probe, while MoS2 nanosheets (MoS2 NSs) serve as both a fluorescence quencher and a photothermal agent. Hyaluronic acid conjugated with Ce6 (HA-Ce6) was assembled on the surface of MoS2 NSs to form MHC NSs. Without the HAase secreted by methicillin-resistant Staphylococcus aureus (MRSA), the fluorescence of Ce6 is quenched by MoS2 NSs, while in the presence of MRSA, HAase can degrade the HA and release Ce6, which restores the fluorescence and photodynamic activity of Ce6. The experimental results show that MHC NSs can fluorescently image the MRSA both in vitro and in vivo by HAase activation. Meanwhile, MHC NSs can serve as PTT/PDT dual-mode antibacterial agents for MRSA. In vitro antibacterial results show that MHC NSs can kill 99.97% MRSA under 635 nm and 785 nm laser irradiation. In vivo study further shows that MHC NSs can kill 99.9% of the bacteria in MRSA infected tissues in mice and prompt wound healing by combined PTT/PDT. This work provides novel HAase-responsive phototheranostic nanoagents for effective detection and treatment of bacterial infections.