Chitosan-based thermosensitive injectable hydrogel with hemostatic and antibacterial activity for preventing breast cancer postoperative recurrence and metastasis via chemo-photothermal therapy

Abstract

Primary resection surgery is a conventional approach in breast cancer treatment, which plays a pivotal role in the prevention of recurrence and metastasis. In this study, an injectable hydrogel comprising chitosan (CS), β-glycerophosphate (β-GP), and dopamine (DA) with near-infrared (NIR) photothermal attributes was developed. The composite hydrogels integrate doxorubicin (DOX), termed DCGD, and can be used for chemotherapy, synergistic photothermal therapy, anti-bacterial and hemostasis. Local administration of injectable DCGD hydrogels into breast cancer resection cavities could prevent the postoperative breast cancer recurrence and metastasis via chemo-photothermal therapy. Additionally, the remarkable hemostatic and anti-bacterial properties of DCGD facilitated postoperative wound healing. Notably, the DCGD hydrogel had a dual pH- and photothermal-responsive DOX release profile, ensuring sustained drug release to residual tumor tissues triggered by NIR laser irradiation and the acidic tumor microenvironment. Histological analyses including H&E, TUNEL, and Ki67 immunohistochemistry confirmed the potent anti-recurrent and anti-metastatic efficacy of DCGD hydrogels. Therefore, the DCDG hydrogels developed in our study had the favorable hemostatic, anti-bacterial, photothermal and drug-loading effects, which provided a new strategy for postoperative breast cancer recurrence and metastasis treatment.

Keywords: Breast cancer; Injectable hydrogel; Metastases; Photothermal; Recurrences.