Rational Design of a Polymer with Robust Efficacy for Intracellular Protein and Peptide Delivery

作者：Hong Chang, Jia Lv, Xin Gao, Xing Wang, Hui Wang, Hui Chen, He Xu, Lei Li, Yiyun Cheng · 发表于：Nano Letters · 年份：2017 · DOI：10.1021/acs.nanolett.6b04955 · 被引用次数：190 · 研究领域：RNA Interference and Gene Delivery、Advanced biosensing and bioanalysis techniques、Dendrimers and Hyperbranched Polymers

The efficient delivery of biopharmaceutical drugs such as proteins and peptides into the cytosol of target cells poses substantial challenges owing to their large size and susceptibility to degradation. Current protein delivery vehicles have limitations such as the need for protein modification, insufficient delivery of large-size proteins or small peptides, and loss of protein function after the delivery. Here, we adopted a rational approach to design a polymer with robust efficacy for intracellular protein and peptide delivery. The polymer is composed of a dendrimer scaffold, a hydrophobic membrane-disruptive region, and a multivalent protein binding surface. It allows efficient protein/peptide binding, endocytosis, and endosomal disruption and is capable of efficiently delivering various biomacromolecules including bovine serum albumin, R-phycoerythrin, p53, saporin, β-galactosidase, and peptides into the cytosol of living cells. Transduction of apoptotic proteins and peptides successfully induces apoptosis in cancer cells, suggesting that the activities of proteins and peptides are maintained during the delivery. This technology represents an efficient and useful tool for intracellular protein and peptide delivery and has broad applicability for basic research and clinical applications.