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

Abstract

AbstractCell 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.