摘要
Current chemotherapies are limited by systemic toxicity and insufficient drug concentrations at the tumor site. Local drug delivery systems (LDDSs) may enhance therapeutic efficacy while minimizing off-target effects. Compared with synthetic polymers, natural polymers have better biocompatibility and biodegradability. Silk fibroin (SF) stands out for its biocompatibility, hypoallergenicity, biodegradability, and controlled sol–gel transitions. In this study, we developed an injectable SF nanocomposite hydrogel incorporating hollow gold nanoparticles (HGNs) and doxorubicin (DOX), in which the HGNs efficiently converted near-infrared (NIR) light into heat, triggering rapid SF gelation. This process entraps HGNs and DOX within the tumor, enabling one-shot multiple photothermal therapy and pH-responsive sustained DOX release for synergistic cancer treatment. In vitro experiments verified the effectiveness of synergistic chemo-photothermal treatment, while in vivo studies in breast cancer models demonstrated that the combined therapy more effectively inhibited tumor growth than either chemotherapy or photothermal therapy alone under repeated NIR irradiation, without tumor regrowth during the observation period. This injectable, light-responsive SF-based LDDS provides a practical platform with strong translational potential for localized treatment of solid tumors. © 2026 Elsevier B.V.