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Genetically Engineered Liposome-like Nanovesicles as Active Targeted Transport Platform.

Abstract
Ligand-targeted delivery of drug molecules to various types of tumor cells remains a major challenge in precision medicine. Inspired by the secretion process and natural cargo delivery functions of natural exosomes, biomimetic synthetic strategies are exploited to prepare biofunctionalized liposome-like nanovesicles (BLNs) that can artificially display a wide variety of targeting protein/peptide ligands and directly encapsulate medical agents for enhanced drug delivery. Here, as a proof of concept, genetically engineered BLNs, which display human epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, are developed to, respectively, target two types of tumor cells. Notably, in comparison to synthetic liposomes covalently coupled with hEGF, it is demonstrated in this work that biosynthetically displayed hEGF ligands on BLNs possess higher biological activities and targeting capabilities. Additionally, treatments with doxorubicin-loaded BLNs displaying Affibody ligands exhibit much better antitumor therapeutic outcomes than clinically approved liposomal doxorubicin (Doxil) in HER2-overexpressing BT474 tumor xenograft models. These data suggest that BLN is suitable as a potent surrogate for conventional proteoliposomes or immunoliposomes as a result of excellent targeting capacities and facile production of BLNs.
AuthorsPengfei Zhang, Long Zhang, Zainen Qin, Suhang Hua, Zhide Guo, Chengchao Chu, Huirong Lin, Yang Zhang, Wengang Li, Xianzhong Zhang, Xiaoyuan Chen, Gang Liu
JournalAdvanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 30 Issue 7 (Feb 2018) ISSN: 1521-4095 [Electronic] Germany
PMID29280210 (Publication Type: Journal Article)
Copyright© 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Ligands
  • Liposomes
  • Peptides
  • Doxorubicin
Topics
  • Cell Line, Tumor
  • Doxorubicin
  • Drug Delivery Systems
  • Humans
  • Ligands
  • Liposomes (chemistry)
  • Nanostructures
  • Neoplasms
  • Peptides

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