Activatable Polymeric STING Agonist-Gold Nanorod Conjugate Driving STING Signaling and Immunogenic Activation in Colorectal Cancer Immunotherapy.

Abstract

Activation of the stimulator of interferon genes (STING) pathway provides a potent route to awaken antitumor immunity, yet its efficacy is limited by inefficient coordination of innate immune signaling and incomplete engagement of the cancer-immunity cycle. Herein, we present an activatable polymeric STING agonist-gold nanorod conjugate (GNR-PEI-M) that amplifies STING signaling and immunogenic activation through a laser-controlled photothermal process, effectively coupling antigen release with molecular immune stimulation. Upon near-infrared (NIR) irradiation, GNR-PEI-M induces localized hyperthermia and immunogenic cell death, releasing tumor-associated antigens that amplify STING signaling and promote dendritic cell maturation. Proteomic analysis confirmed that this coordinated cascade promoted type I interferon production, antigen presentation, and T-cell responses, resulting in 96.1% tumor regression in MC38 models without systemic toxicity. This study demonstrates a precisely controllable nanoplatform that couples photothermal excitation with polymeric immune activation to achieve an effective and well-tolerated cancer immunotherapy.