Win–Win Integration of Genetically Engineered Cellular Nanovesicles with High-Absorbing Multimodal Phototheranostic Molecules for Boosted Cancer Photo-Immunotherapy

Photo-immunotherapy is one of the most promising cancer treatment strategies. As immunotherapeutic agents, immune checkpoint blockade antibodies against programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) exhibit substantial potential, but have to face non-specific distribution and the subsequent immune-related adverse events. Meanwhile, high-performance phototheranostic agents concurrently possessing multiple phototheranostic modalities and high light-harvesting capacity are really attractive and highly desired as touching phototheranostic modules. Herein, a win–win strategy that integrates phototheranostic molecule design and targeted immunotherapeutic module preparation is developed to construct high-powered photo-immunotherapy systems. Specifically, the phototheranostic agent (AOTTIT) displaying typical aggregation-induced fluorescence extending to the second near-infrared II window, as well as outstanding reactive oxygen species and heat production capacity is first obtained via ingenious design. Notably, AOTTIT exhibits a record high molar extinction coefficient among the reported organic multimodal phototheranostic molecules. Meanwhile, PD-1 genetically engineered cancer cell membrane-derived nanovesicles (PD-1/CMNVs) are prepared as both nanocarriers and immunotherapeutic agents to camouflage AOTTIT nanoparticles, yielding a multifunctional photo-immunotherapeutic agent (CMNPs/PD-1) with tumor-specific active and homologous targeting ability. The distinct suppression of primary and metastatic lung tumors after only once treatment to the primary tumor substantiated the synergistically strengthened photo-immunotherapeutic efficiency of this win-win strategy.