Multi-Catcher Polymers Regulate the Nucleolin Cluster on the Cell Surface for Cancer Therapy

作者全名："Cheng, Feng; Jiang, Yongjian; Kong, Bo; Lin, Huarong; Shuai, Xinjia; Hu, Pingping; Gao, Pengfei; Zhan, Lei; Huang, Chengzhi; Li, Chunmei"

作者地址："[Cheng, Feng; Jiang, Yongjian; Kong, Bo; Lin, Huarong; Shuai, Xinjia; Gao, Pengfei; Zhan, Lei; Huang, Chengzhi; Li, Chunmei] Southwest Univ, Southwest Univ, Coll Pharmaceut Sci, Key Lab Luminescence Anal & Mol Sensing,Minist Edu, Chongqing 400715, Peoples R China; [Hu, Pingping] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China"

通信作者："Li, CM (通讯作者)，Southwest Univ, Southwest Univ, Coll Pharmaceut Sci, Key Lab Luminescence Anal & Mol Sensing,Minist Edu, Chongqing 400715, Peoples R China."

来源：ADVANCED HEALTHCARE MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000971856600001

JCR分区：Q1

影响因子：10

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：cancer therapy; ligand-receptor regulation; membrane anchoring; multi-catcher polymers

摘要："Cell signal transduction mediated by cell surface ligand-receptor is crucial for regulating cell behavior. The oligomerization or hetero-aggregation of the membrane receptor driven by the ligand realizes the rearrangement of apoptotic signals, providing a new ideal tool for tumor therapy. However, the construction of a stable model of cytomembrane receptor aggregation and the development of a universal anti-tumor therapy model on the cellular surface remain challenging. This work describes the construction of a ""multi-catcher"" flexible structure GC-chol-apt-cDNA with a suitable integration of the oligonucleotide aptamer (apt) and cholesterol (chol) on a polymer skeleton glycol chitosan (GC), for the regulation of the nucleolin cluster through strong polyvalent binding and hydrophobic membrane anchoring on the cell surface. This oligonucleotide aptamer shows nearly 100-fold higher affinity than that of the monovalent aptamer and achieves stable anchoring to the plasma membrane for up to 6 h. Moreover, it exerts a high tumor inhibition both in vitro and in vivo by activating endogenous mitochondrial apoptosis pathway through the cluster of nucleolins on the cell membrane. This multi-catcher nano-platform combines the spatial location regulation of cytomembrane receptors with the intracellular apoptotic signaling cascade and represents a promising strategy for antitumor therapy."

基金机构：National Natural Science Foundation of China (NSFC) [22074124]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0521]; Fundamental Research Funds for the Central Universities [XDJK2020TY001]; Chongqing Talents Program for Outstanding Scientists [cstc2021ycjh-bgzxm0179]

基金资助正文："This work was financially supported by the National Natural Science Foundation of China (NSFC, No. 22074124), Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0521), the fund of Fundamental Research Funds for the Central Universities (XDJK2020TY001) and Chongqing Talents Program for Outstanding Scientists (No.cstc2021ycjh-bgzxm0179)."