Wang Rong, Hu Qiaoying, Huang Susu, Fang Yuelin, Kong Xinru, Kaur Prabhleen, Zhang Jicheng, Wang Yanqing, Liu Dongzhu, Wu Hang, Li Yingying, Ji Jianbo, Yang Xiaoye, Ye Lei, Zhai Guangxi
NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
ACS Appl Mater Interfaces. 2024 Jan 24;16(3):4071-4088. doi: 10.1021/acsami.3c17017. Epub 2024 Jan 9.
Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.
手术切除仍然是肿瘤治疗最常用的方法;然而,术后高复发和转移问题亟待解决。在此,我们报道了一种基于“硫醇-烯”点击化学的可注射两性离子水凝胶,其包含阿霉素(DOX)以及巨噬细胞膜(MM)包裹的负载1-甲基色氨酸(1-MT)的聚酰胺-胺树枝状大分子(P-DOX/1MT),用于预防肿瘤术后复发。结果表明,P-DOX/1MT@MM表现出肿瘤细胞对树枝状大分子的识别和摄取增强,并诱导免疫原性细胞死亡。在小鼠肿瘤模型中,P-DOX/1MT@MM-Gel表现出高治疗效率,可显著降低肿瘤复发,包括抑制肿瘤生长、促进树突状细胞成熟以及增加肿瘤浸润性细胞毒性T淋巴细胞。机制分析表明,该水凝胶大大降低了对正常组织的副作用,并显著提高了其治疗效果。水凝胶中的1MT释放更快,改善了肿瘤抑制微环境并增加了肿瘤细胞对DOX的敏感性。然后,P-DOX/1MT@MM中的DOX有效消除了残留肿瘤细胞并发挥了增强的毒性作用。总之,这种结合化疗和免疫疗法的新型可注射水凝胶具有顺序释药特性,是预防肿瘤术后复发的一种有前景的策略。
ACS Appl Mater Interfaces. 2021-10-6