Zhou Chaopei, Dong Xiuxiu, Song Chunxiang, Cui Shuang, Chen Tiantian, Zhang Daji, Zhao Xiuli, Yang Chunrong
College Pharmacy, Jiamusi University, Jiamusi, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Front Bioeng Biotechnol. 2021 Mar 10;9:653417. doi: 10.3389/fbioe.2021.653417. eCollection 2021.
The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8 T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.
联合疗法的应用突破了单一疗法的局限性，为肿瘤治疗带来了更好的临床效益。在此，构建了一种基于透明质酸/普朗尼克F68的共聚物混合胶束，用于化疗药物多西他赛（PHDM）与程序性细胞死亡配体-1（PD-L1）抗体的靶向递送。当将PHDM+抗PD-L1注入血液系统时，PHDM可通过CD44介导的内吞作用积聚到肿瘤部位并靶向肿瘤细胞，从而实现肿瘤化疗。而抗PD-L1可靶向肿瘤细胞表面表达的PD-L1蛋白，具有肿瘤免疫治疗的免疫检查点阻断特性。该策略不仅可以直接杀死肿瘤细胞，还可以提高CD8 T细胞水平并促进效应细胞因子的释放。总之，合理设计的PHDM+抗PD-L1治疗策略为肿瘤免疫化疗开辟了一条新途径。
