Dual-functional alginate and collagen-based injectable hydrogel for the treatment of cancer and its metastasis.

BACKGROUND: Immunotherapies have been gaining attention for the prevention of cancer recurrence and metastasis. Cancer immunotherapy can induce memory cells to target cancer-specific antigens and, thus, selectively kill cancer cells. However, there are difficulties in inducing cancer antigen-specific immunity due to limited knowledge regarding cancer antigens. In this study, we synthesized a dual-functional hydrogel to induce antigen generation and immune activation. RESULTS: To elicit a cancer self-antigen-specific immune response, we synthesized an alginate-collagen-based injectable hydrogel, called thermally responsive hydrogel (pTRG), which was incorporated with indocyanine green and the immune stimulator polyinosinic:polycytidylic acid (poly I:C). pTRG was evaluated for its anticancer and anti-metastatic effects against CT-26 carcinoma and 4T1 breast tumor in mice by combining photothermal therapy (PTT) and immunotherapy. Near-infrared (NIR) irradiation promoted temperature elevation in pTRG, consequently exerting a therapeutic effect on mouse tumors. Lung metastasis was prevented in cured CT-26 tumor-injected mice following pTRG treatment via cancer antigen-specific T cell immunity. Moreover, pTRG successfully eliminated the original tumor in 4T1 tumor-bearing mice via PTT and protected them from lung metastasis. To further evaluate the carrier function of TRGs, different types of immunotherapeutic molecules were incorporated into TRGs, which led to the effective elimination of the first CT-26 tumor and the prevention of lung metastasis. CONCLUSIONS: Our data demonstrate that TRG is a efficient material not only for treating primary tumors but also for preventing metastasis and recurrence.