Biomimetic Metallacage\nNanoparticles with Aggregation-Induced\nEmission for NIR-II Fluorescence Imaging-Guided Synergistic Immuno-Phototherapy\nof Tumors

The integration of theranostics, which combines diagnostics\nwith\ntherapeutics, has markedly improved the early detection of diseases,\nprecise medication management, and assessment of treatment outcomes.\nIn the realm of oncology, organoplatinum-based supramolecular coordination\ncomplexes (SCCs) that can coload therapeutic agents and imaging molecules\nhave emerged as promising candidates for multimodal theranostics of\ntumors. To address the challenges of tumor-targeted delivery and multimodal\ntheranostics for SCCs, this study employs a cell membrane cloaking\nstrategy to fabricate biomimetic metallacage nanoparticles (MCNPs)\nwith multimodal imaging capabilities and homologous targeting capabilities.\nSpecifically, a photosensitizer molecule (BTTP) containing AIE-active\ngroups was assembled into a metallacage of C-BTTP through Pt–N\ncoordination. This process endows the metallacage with strong NIR-II\nfluorescence in the aggregated state and significantly superior ROS\ngeneration compared to that of the precursor ligand. After being encapsulated\nwith F127, the MCNPs were further cloaked with U87 cancer cell membranes,\ncreating biomimetic MCNPs that achieve tumor-targeting capabilities.\nVerified by in vitro and in vivo experiments, MCNPs enable multimodal\nimaging and initiate immunotherapy under photothermal and photodynamic\nstimulation, leading to synergistic antitumor effects. Furthermore,\nthe evaluation of immunogenic cell death and dendritic cell maturation\nrate in U87 tumor-bearing mice confirmed the mechanism of photothermal\nand photodynamic synergistic immunotherapy. This study provides an\ninnovative strategy for enhancing the tumor-targeting and therapeutic\nefficiency of SCCs, offering a versatile strategy for efficient and\nminimally invasive theranostics of tumors. The development of such\nbiomimetic nanoparticles represents a significant advancement in the\nfield of nanomedicine, potentially transforming cancer treatment through\npersonalized and targeted therapies.