文献类型：期刊文献

英文题名：Sialidase-Conjugated "NanoNiche" for Efficient Immune Checkpoint Blockade Therapy

作者：Zhou, Ze-Rui[1];Wang, Xiao-Yuan[1];Jiang, Lei[1];Li, Da-Wei[1];Qian, Ruo-Can[1]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Sch Chem & Mol Engn, Key Lab Adv Mat, Shanghai 200237, Peoples R China

年份：2021

卷号：4

期号：7

起止页码：5735

外文期刊名：ACS APPLIED BIO MATERIALS

收录：EI(收录号：20213010676549);WOS:【ESCI(收录号:WOS:000675478800033)】；

基金：This research was supported by the National Natural Science Foundation of China (21977031), the National Science and Technology Major Project of China (2018ZX10302205), the Shanghai Science and Technology Committee (19ZR1472300), and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：molecular imprinting; immune checkpoint therapy; NanoNiche; PD-L1; sialoglycans

摘要：Reactivation of T-cell immunity by blocking the PD-1/PD-L1 immune checkpoint has been considered a promising strategy for cancer treatment. However, the recognition of PD-L1 by antibodies is usually suppressed due to the N-linked glycosylation of PD-L1. In this study, we present an effective PD-L1-blocking strategy based on a sialidase-conjugated "NanoNiche" to improve the antitumor effect via T-cell reactivation. Molecularly imprinted by PD-L1 N-glycans, NanoNiche can specifically recognize glycosylated PD-L1 on the tumor cell surface, thereby resulting in more efficient PD-L1 blockade. Moreover, sialidase modified on the surface of NanoNiche can selectively strip sialoglycans from tumor cells, enhancing immune cell infiltration. In vitro studies confirmed that NanoNiche can specifically bind with PD-L1 while also desialylate the tumor cell surface. The proliferation of PD-L1-positive MDA-MB-231 human breast cancer cells under T-cell killing was significantly inhibited after NanoNiche treatment. In vivo experiments in solid tumors show enhanced therapeutic efficacy. Thus, the NanoNiche-sialidase conjugate represents a promising approach for immune checkpoint blockade therapy.