title: Rational Design of a Polymer with Robust Efficacy for Intracellular Protein and Peptide Delivery.
abstract: 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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University , Shanghai, 200003, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, P. R. China.
authors.forename: Yiyun
authors.identifier: 0000-0002-1101-5692
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D011506:Proteins
keywords: Rational design; peptide delivery; polymer; protein delivery; robust efficacy