Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating and nuclear accumulation

Xinghong Duo, Lingchuang Bai, Jun Wang, Jintang Guo, Xiangkui Ren, Shihai Xia, Wencheng Zhang, Abraham Domb, Yakai Feng

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Gene therapy has drawn great attention in the treatments of many diseases, especially for cardiovascular diseases. However, the development of gene carriers with low cytotoxicity and multitargeting function is still a challenge. Herein, the multitargeting REDV-G-TAT-GNLS peptide was conjugated to amphiphilic cationic copolymer poly(ε-caprolactone-co-3(S)-methyl-morpholine-2,5-dione)-g-polyethyleneimine (PCLMD-g-PEI) via a heterobifunctional orthopyridyl disulfide-poly(ethylene glycol)-N-hydroxysuccinimide (OPSS-PEG-NHS) linker to prepare PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers with the aim to develop the gene carriers with low cytotoxicity and high transfection efficiency. The multitargeting micelles were prepared from PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers by selfassembly method and used to load pEGFP-ZNF580 plasmids (pDNA) to form gene complexes for enhancing the proliferation and migration of endothelial cells (ECs). The loading pDNA capacity was proved by agarose gel electrophoresis assay. These multitargeting gene complexes exhibited low cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The high internalization efficiency of these gene complexes was confirmed by flow cytometry. The results of in vitro transfection demonstrated that these multitargeting gene complexes possessed relatively high transfection efficiency. The rapid migration of ECs transfected by these gene complexes was verified by wound healing assay. Owing to ECs-targeting ability, cell-penetrating ability and nuclear targeting capacity of REDV-G-TAT-G-NLS peptide, the multitargeting polycationic gene carrier with low cytotoxicity and high transfection efficiency has great potential in gene therapy.[Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)889-901
Number of pages13
JournalFrontiers of Chemical Science and Engineering
Volume14
Issue number5
DOIs
StatePublished - 1 Oct 2020
Externally publishedYes

Bibliographical note

Funding Information:
This project was supported by the National Natural Science Foundation of China (Grant Nos. 51673145, 51873149, 21875157 and 51963018), the National Key Research and Development Program of China (Grant No. 2016YFC1100300), the International Science and Technology Cooperation Program of China (Grant No. 2013DFG52040).

Publisher Copyright:
© 2020, Higher Education Press.

Keywords

  • ECs
  • gene carriers
  • multitargeting function
  • transfection efficiency

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