<i>In Situ</i> Implantation of Chitosan Oligosaccharide-Doped Lipoic Acid Hydrogel Breaks the “Vicious Cycle” of Inflammation and Residual Tumor Cell for Postoperative Skin Cancer Therapy

Abstract

Surgical excision is the main treatment for skin cancer, but the tumor recurrence caused by the "vicious cycle" between residual tumor cells and postoperative inflammation remains a challenge. Herein, a new material, which can break the "vicious cycle", was developed by incorporating chitosan oligosaccharides into lipoic acid hydrogel (COS@LA-hydrogel). When implanted at the resection site, the COS@LA-hydrogel would have a sustained release of LA and COS, which could not only kill residual tumor cells by synergistically reducing AKT phosphorylation but also decrease inflammation by inhibiting the expression of tumor necrosis factor-α (TNF-α) and inhibiting bacterial infection, respectively. As a proof of concept, in the postoperative melanoma resection model, the COS@LA-hydrogel reduced the expression of pro-inflammatory factors TNF-α and interleukin-6 (IL-6) by up to 78 and 80%, respectively, and they showed almost no tumors and the median survival of the mice was 2.5 times longer than that of the control group. The hydrogel with the function of "vicious cycle" breaking holds clinical potential.