An adhesive hydrogel implant combining chemotherapy and tumor microenvironment remodeling for preventing postoperative recurrence and metastasis of breast cancer

Postoperative tumor microenvironments, such as cancer-associated adipocytes and angiogenesis, severely affect the recurrence and metastasis of residual tumor cells. Efficiently killing residual tumor cells and simultaneously blocking the function of cancer-associated adipocytes and inhibiting angiogenesis might be a promising strategy to prevent postoperative tumor recurrence and metastasis. Here, a bio-adhesive hydrogels grafting dopamine and 3-aminobenzeneboronic acid onto hyaluronic acid were facilely developed to load anticancer drug doxorubicin and metformin (DOX/Met@HDP) for postoperative in-situ treatment in breast cancer. After implantation into the tumor surgical cavity, DOX/Met@HDP persistently retains drugs at the tumor resection sites and releases drugs in a tumor acidic microenvironment-controlled manner. The released doxorubicin efficiently kills residual tumor cells, while the released metformin inhibits adipocyte function to abrogate the adipocyte-promoted proliferation and migration of tumor cells and suppresses tumor angiogenesis, resulting in the significant inhibition of postoperative tumor recurrence and metastasis. Our results demonstrate that DOX/Met@HDP is a potential implant for improving the prognosis of breast cancer patients undergoing surgery.