Journal
NANO LETTERS
Volume 17, Issue 3, Pages 1678-1684Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.6b04955
Keywords
Rational design; polymer; robust efficacy; protein delivery; peptide delivery
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Funding
- National Natural Science Foundation of China [21474030, 21322405]
- Shanghai Municipal Science and Technology Commission [17XD1401600, 148014518]
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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 albumin, R-phycoerythrin, p53, saporin, beta-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.
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