Photoresponsive Carbon Dot Hydrogel for miR-155-Driven Immune Remodeling in Breast Cancer

A robust, photo-responsive hydrogel was engineered to offer a promising strategy for achieving photothermal effects, spatiotemporal control of therapeutic release, and strong adhesive properties. Here, red-emissive carbon dots (CD) and G3 poly(amidoamine) dendrimers (PAMAM) were self-assembled to produce CD@PAMAM, and a polyelectrolyte hydrogel was prepared using tragacanth gum (TG) and trimethyl chitosan (TMC). CD@PAMAM cross-linked within the TG-TMC hydrogel generates crystalline domains that improve nucleation, adhesion, and mechanical integrity, while enabling effective miR-155 loading and synergistic immune modulation via its photodynamic activity. Hydrogels exhibit displayed robust mechanical integrity, including tensile strength up to 176 kPa, lap shear strength 257.6 kP, and elastic modulus of 120 kPa, as well as control good swelling resistance, which is highly suitable for soft tissue adhesion. It also shows strong adhesion over various tissues, generating molecular oxygen in the tumor hypoxia region. Under near-infrared (NIR) irradiation, hydrogel efficiently generated photothermal 52 °C and singlet oxygen (¹O₂) levels for CD@PAMAM-TG-TMC/miR-155 under NIR showed 75% depletion in 10 min, and the coupled photothermal-photodynamic effects triggered immunogenic cell death. In the tumor-induced mouse model, hydrogel controls tumor growth to 87.2% in 10 min and photo-activation of CD@PAMAM damages cancer cells, releasing damage-associated molecular patterns (DAMPs). The elevated levels of HMGB1, ATP, CRT, and inflammatory cytokines promoted the dendritic cell maturation and elicited durable systemic immune memory, underscoring its capacity to eradicate tumors and reduce recurrence risk. The resulting CD@PAMAM hydrogel exhibits strong adhesion, mechanical robustness, efficient photothermal heating, and enhanced singlet oxygen generation under NIR irradiation. This modular and translatable photo-responsive platform enables precise combination therapy, thereby potentiating the antitumor immune response.