Carrier-Free Ce6&SR717 Nanomedicine Enables Abscopal Photoimmunotherapy via cGAS-STING Activation in Breast Cancer.

Potent STING agonists are among the most promising strategies for reversing immunosuppression in "cold" tumors, but in vivo antitumor efficacy is frequently limited by dose-limiting systemic toxicity and inadequate tumor selectivity. To achieve localized STING activation and robust systemic immunity, we combined STING agonism with photodynamic therapy (PDT), creating a carrier-free nanoplatform (Ce6&SR717 NPs) through self-assembly of SR717 (STING agonist) and Ce6 (chlorin e6, photosensitizer). This excipient-free design achieves maximum drug loading, alleviates carrier-related safety issues, and realizes the spatiotemporally synchronized activation of PDT-induced immunogenic cell death and STING signaling through irradiation, which establishes an auto-amplifying cycle of on-site antigen release and systemic immune priming. In the murine breast cancer model, Ce6&SR717 NPs plus laser irradiation dramatically increased CD8+ T-cell infiltration within the tumor, triggered strong systemic antitumor immunity, and suppressed both primary and distant tumors. Collectively, these results identify Ce6&SR717 NPs as a safe and efficient modality for synergistic photo-immunotherapy of immunologically cold tumors.