An imaging-guided self-amplifying photo-immunotherapeutic nanoparticle for STING pathway activation and enhanced cancer therapy
Qiaoqi Chen, Huilin Yu, Nianwu Li, Hua Zhang, Mixiao Tan, Weiwei Liu, Min Zheng, Yaqin Hu, Long Cheng, Yushi Chen, Haitao Ran, Qiu Zeng, Yuan Guo
Abstract
The stimulator of interferon genes (STING) pathway is a promising target in cancer immunotherapy. However, current nanomedicine strategies targeting the STING pathway often suffer from limited tumor specificity and insufficient immune activation. In this study, we developed a novel imaging-guided, self-amplifying photo-immunotherapeutic nanoparticle (SSCOL), comprising a liposome framework that encapsulates the phase-change material perfluoropentane (PFP), the photothermal agent superparamagnetic iron oxide (SPIO), and the STING agonist cGAMP. This nanoparticle exhibits excellent photoacoustic/ultrasound dual-modal imaging capability, enabling precise visualization of tumor tissue. CREKA enables specific binding to fibrin-fibronectin complexes in the tumor stroma, while NIR-induced photothermal effects of SPIO trigger coagulation, amplifying target formation and enhancing nanoparticle accumulation via a positive feedback mechanism. Under photothermal therapy, the phase transition of SSCOL enables the controlled and efficient release of the encapsulated cGAMP, which subsequently activates the STING pathway and triggers a pro-inflammatory cascade, enhances dendritic cell maturation and cytotoxic T lymphocyte activation, and elicits robust immune responses against both primary and metastatic tumors. Collectively, this multifunctional nanoparticle offers a promising strategy that integrates imaging, targeting, and photothermal-enhanced immune activation for STING-mediated cancer immunotherapy.