Injectable thermosensitive microsphere-hydrogel composite system:combined therapy of hepatocellular carcinoma by remodeling tumor immune microenvironment

可注射温敏微球-水凝胶复合系统:通过重塑肿瘤免疫微环境联合治疗肝细胞癌

Advanced hepatocellular carcinoma(HCC)is one of the most prevalent malignancies,and the clinical treatment outcomes are not satisfactory.Due to the complexity,heterogeneity,and immunosuppressive microenvironment of HCC,monotherapies have limited effects.Therefore,combined therapy may effectively enhance antitumor treatment by remodeling the tumor immune microenvironment.This study reports an injectable thermosensitive microsphere-hydrogel composite system for local co-delivery of the targeted drug sorafenib(SOR)and immunomodulatory cytokines for the combined therapy of HCC.The delivery system exhibited superior properties such as dual-drug delivery,sustained and slow release,local injectability,thermosensitivity,and low side effects.Moreover,it successfully remodeled the immune microenvironment of HCC by increasing the infiltration of CD8^(+)T cells and natural killer cells while decreasing the infiltration of immunosuppressive Treg cells,thereby achieving a potent synergistic effect with SOR.This safe composite delivery system can remodel the tumor microenvironment and enhance anti-tumor treatment,providing a valuable option for the treatment of HCC.

晚期肝细胞癌(HCC)是最常见的恶性肿瘤之一,但临床治疗效果并不理想.由于HCC的复杂性、异质性和免疫抑制微环境的影响,单一药物疗法效果有限.联合治疗可能通过调节肿瘤免疫微环境,有效增强抗肿瘤治疗.本研究报道了一种可注射的温敏微球-水凝胶复合系统,局部共递送靶向药物索拉非尼(SOR)和免疫调节细胞因子用于HCC的联合治疗.该递送系统具有双药物传递、持续缓释、局部可注射性、温敏性和体内副作用低等优越特性.此外,该递送系统成功重塑了HCC的免疫微环境,增加了免疫效应CD8^(+)T细胞和NK细胞的浸润,减少了免疫抑制性Treg细胞的浸润,与SOR联合发挥抗肿瘤作用.这种安全的复合递送系统可以重塑肿瘤微环境,增强抗肿瘤效果,为HCC治疗提供了一个有价值的选择.