Injectable thermosensitive hydrogel to enhance the photothermal ablation and systemic immunotherapy of breast tumors

Abstract

As the high-frequency tumor in women around the world, breast cancer has high mortality due to metastasis tumors making it difficult to cure. Herein, we report a near-infrared (NIR) activated bio-multifunctional thermosensitive hydrogel (denoted as AMDR) with powerful cell killing and immunogenicity amplifying ability. Based on the molecular engineering strategy, a photothermal agent (M-4) with 52.4% conversion efficiency was synthesized. Accordingly, the designed injectable thermosensitive hydrogel AMDR is simply fabricated by the employment of the M-4 photothermal agent, doxorubicin hydrochloride (DOX) as the antitumor drug, and imiquimod (R837) as the immunologic adjuvant by self-assembly. Under NIR irradiation, the AMDR hydrogel can generate local mild heat to release DOX for synergistic killing of tumor cells with little damage to normal cells. The immunogenic cell death induced by potent in situ killing combined with heat-released R837 can trigger robust immune response to inhibit and kill metastasis tumors. The developed AMDR hydrogel is successfully applied in the treatment of primary tumors and inhibition of distal tumors of tumor-bearing mice. The study provides a novel strategy and platform for complete treatment of breast cancer and also offers ideas for designing high-efficiency photothermal agents.