Biomimetic Metallacage Nanoparticles with Aggregation-Induced Emission for NIR-II Fluorescence Imaging-Guided Synergistic Immuno-Phototherapy of Tumors.

Abstract

The integration of theranostics, which combines diagnostics with therapeutics, has markedly improved the early detection of diseases, precise medication management, and assessment of treatment outcomes. In the realm of oncology, organoplatinum-based supramolecular coordination complexes (SCCs) that can coload therapeutic agents and imaging molecules have emerged as promising candidates for multimodal theranostics of tumors. To address the challenges of tumor-targeted delivery and multimodal theranostics for SCCs, this study employs a cell membrane cloaking strategy to fabricate biomimetic metallacage nanoparticles (MCNPs) with multimodal imaging capabilities and homologous targeting capabilities. Specifically, a photosensitizer molecule (BTTP) containing AIE-active groups was assembled into a metallacage of C-BTTP through Pt-N coordination. This process endows the metallacage with strong NIR-II fluorescence in the aggregated state and significantly superior ROS generation compared to that of the precursor ligand. After being encapsulated with F127, the MCNPs were further cloaked with U87 cancer cell membranes, creating biomimetic MCNPs that achieve tumor-targeting capabilities. Verified by in vitro and in vivo experiments, MCNPs enable multimodal imaging and initiate immunotherapy under photothermal and photodynamic stimulation, leading to synergistic antitumor effects. Furthermore, the evaluation of immunogenic cell death and dendritic cell maturation rate in U87 tumor-bearing mice confirmed the mechanism of photothermal and photodynamic synergistic immunotherapy. This study provides an innovative strategy for enhancing the tumor-targeting and therapeutic efficiency of SCCs, offering a versatile strategy for efficient and minimally invasive theranostics of tumors. The development of such biomimetic nanoparticles represents a significant advancement in the field of nanomedicine, potentially transforming cancer treatment through personalized and targeted therapies.