Tumor microenvironment-responsive versatile "Trojan horse" theranostic nanoplatform for magnetic resonance imaging-guided multimodal synergistic antitumor treatment

A natural killer (NK)-92 cell membrane-camouflaged mesoporous MnO₂-enveloped Au@Pd (Au@Pd@MnO₂) nanoparticles (denoted as APMN NPs)-based versatile biomimetic theranostic nanoplatform was developed for magnetic resonance (MR) imaging-guided multimodal synergistic antitumor treatments. In this core-shell nanostructure, an Au@Pd core induced near-infrared (NIR)-activatable hyperthermal effects and nanozyme catalytic activity, while a mesoporous MnO₂ shell not only afforded a high drug-loading capability, tumor microenvironment (TME)-triggered MR imaging and drug release, but also endowed catalase-, glutathione peroxidase-, and Fenton-like activities. Furthermore, the NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein-mediated tumoral uptake property. The doxorubicin-loaded APMN (D-APMN) NPs exhibited TME-responsive drug release properties. Furthermore, the cellular uptake, in vivo MR imaging, and NIR thermal imaging confirmed the active tumor-targeting capability and TME-responsive MR imaging property of these biomimetic NPs. An antitumor efficacy test, histological analyses, and blood biochemical profiles suggested that the developed D-APMN NPs possessed a high antitumor activity and biosafety in tumor-bearing nude mice. Therefore, the developed APMN NPs held great potential as an intelligent and comprehensive theranostic nanoplatform for tumor-specific bioimaging and TME-responsive multimodality treatment based on photothermal therapy, chemodynamic therapy, and chemotherapy. STATEMENT OF SIGNIFICANCE: Exploring intelligent and comprehensive theranostic nanoplatforms to integrate tumor-specific bioimaging and TME-responsive multimodal therapy effectively is a challenge. Herein, we successfully developed a new kind of NK-92 cell membrane-camouflaged mesoporous MnO₂-enveloped Au@Pd nanoparticles (APMN NPs)-based versatile biomimetic theranostic nanoplatform for the potential MR imaging-guided multimodal synergistic antitumor treatments. These NPs could integrate unique structural, optical, multiple-catalytic, paramagnetic, and biological merits of NK-92 cell membrane, Au@Pd cores and mesoporous MnO₂ shell in a single nanoplatform. The NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein-mediated tumoral uptake property. The new information obtained from this study may be beneficial to promote the development of novel TME-responsive versatile "Trojan horse" theranostic nanoplatforms for efficient MR imaging-guided multimodal synergistic treatment.