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

Abstract 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.