Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, 210008, P. R. China.
Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, 210008, P. R. China.
Adv Sci (Weinh). 2022 May;9(15):e2105894. doi: 10.1002/advs.202105894. Epub 2022 Mar 25.
Nano-based immunotherapy of therapeutic biomolecules is attractive but tremendously hampered by the poor delivery efficiency. This study reports a novel delivery system of fluorinated-coordinative-epigallocatechin gallate (EGCG), referring as FEGCG/Zn, through the integration of fluorination and zinc ions (Zn ) into EGCG. The robust therapeutics of FEGCG/Zn are measured in terms of the regulating effect on programmed cell death ligand 1 (PD-L1), the effective delivery of diverse biomolecules, and the hitchhiking ability using living cells. Taking small interfering RNA of PD-L1 (siPD-L1) and erythrocytes as an example, the fabricated biomimetic system achieves excellent siPD-L1 delivery and further improves siPD-L1 accumulation in tumors. Finally, the combination of FEGCG/Zn and siPD-L1 promotes antitumor immunotherapy through alleviation of T cells exhaustion by regulating PD-L1 expression in tumor cells. The results demonstrate that FEGCG/Zn substantially regulates PD-L1 expression and improves immune-biomolecule delivery by forming biomimetic nanoassemblies, offering a versatile platform for cancer immunotherapy.
基于纳米的治疗性生物分子免疫疗法很有吸引力，但由于递送效率差而受到极大阻碍。本研究通过将氟原子和锌离子（Zn ）整合到表没食子儿茶素没食子酸酯（EGCG）中，报道了一种新型的氟配位表没食子儿茶素没食子酸酯（EGCG）的递送系统，简称 FEGCG/Zn。FEGCG/Zn 的强大治疗效果是通过调节程序性细胞死亡配体 1（PD-L1）、有效递送多种生物分子以及利用活细胞的搭便车能力来衡量的。以小干扰 RNA 的 PD-L1（siPD-L1）和红细胞为例，所构建的仿生系统实现了优异的 siPD-L1 递送，并进一步提高了 siPD-L1 在肿瘤中的积累。最后，FEGCG/Zn 与 siPD-L1 的结合通过调节肿瘤细胞中 PD-L1 的表达来减轻 T 细胞衰竭，从而促进抗肿瘤免疫治疗。结果表明，FEGCG/Zn 通过形成仿生纳米组装体，显著调节 PD-L1 表达并改善免疫生物分子的递送，为癌症免疫治疗提供了一个多功能平台。
