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Progress in Chemistry 2019, Vol. 31 Issue (2/3): 300-310 DOI: 10.7536/PC180621 Previous Articles   Next Articles

Multifunctional Gene Delivery Systems to Promote the Proliferation of Endothelial Cells

Lingchuang Bai1, Jing Zhao1, Yakai Feng1,2,**()   

  1. 1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
    2. Collaborative Innovation Center of Chemical Science and Chemical Engineering(Tianjin), Tianjin University, Tianjin 300072, China
  • Received: Online: Published:
  • Contact: Yakai Feng
  • About author:
    ** E-mail:
  • Supported by:
    National Key R&D Program of China(2016YFC1100300); National Natural Science Foundation of China(31370969); National Natural Science Foundation of China(51673145); National Natural Science Foundation of China(51873149)
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Artificial vascular grafts play an important role in the clinical treatment of cardiovascular diseases due to the lack of autografts. Artificial vascular grafts, especially for small-diameter artificial vascular grafts, usually encounter the problems such as in-stent restenosis, thus limiting their application in clinical treatment. Endothelialization of artificial vascular grafts can improve their hemocompatibility and maintain their long-term patency. It has been confirmed that multifunctional gene delivery systems can promote the proliferation of vascular endothelial cells(ECs) and help achieve the rapid endothelialization of artificial vascular grafts. Recently, functional peptides and cationic polymers have provided an effective approach for the development of low-toxic and highly efficient multifunctional gene delivery systems. In this review, functional peptides, target genes and polycationic gene carriers used in the transfection of vascular ECs are detailedly introduced. Based on polycationic gene carriers, the current development of multifunctional step-by-step targeting gene delivery systems for promoting the proliferation of ECs and endothelialization are highlighted. Finally, some perspectives on achieving rapid endothelialization via gene transfection are also presented.

Key words: artificial vascular graft, endothelialization, gene delivery system, functional peptide, gene carrier
Fig. 1 Chemical structures of representative cationic polymers
Fig. 2 Synthesis route of modified PEI gene carriers based on 3(S)-methyl-morpholine-2,5-dione copolymers[71]. Reproduced with permission from copyright(2014) Elsevier.
Fig. 3 Synthesis route of mPEG-b-PLGA-g-PEI-CREDVW[79]. Reproduced with permission from copyright(2015) American Chemical Society.
Fig. 4 In vitro vessel formation assay of CAG modified targeting gene complexes.(A) PEI-PLGA/pZNF580,(B) PEG-PEI-PLGA/pZNF580,(C) CAGW-PPP1/pZNF580,(D) CAGW-PPP2/pZNF580,(E) PEI(25 kDa)/pZNF580,(F) non-treated HUVECs,(G) pZNF580[84]. Reproduced with permission from copyright(2017) American Chemical Society.
Fig. 5 In vivo neovascularization assay of CAG modified targeting gene complexes. The results of H&E(1) and immunohistochemical staining with anti-CD31(2).(A) PEI-PLGA/pZNF580,(B) PEG-PEI-PLGA/pZNF580,(C) CAGW-PPP1/pZNF580,(D) CAGW-PPP2/pZNF580,(E) PEI(25 kDa)/pZNF580,(F) pZNF580[84]. Reproduced with permission from copyright(2017) American Chemical Society.
Fig. 6 In vitro transfection of CAG modified star-shaped targeting gene complexes. (A)Nontreated ECs,(B)PLGA-g-PEI/pDNA,(C) PLGA-g-PEI-CAGW/pDNA,(D) PEI 10 kDa/pDNA,(E) PLGA-g-PEI-CAGW/pDNA treated SMCs[85]. Reproduced from an open access journal from MDPI publication.
Fig. 7 The formation of multifunctional gene complexes and the illustration of gene delivery to ECs[91]. Reproduced from an open access journal from BMC publication.
Fig. 8 CLSM fluorescence images of the intracellular transport of ternary gene complexes[93]. Reproduced with permission from copyright(2016) John Wiley and Sons.
Fig. 9 Synthesis route of eight-arm and star-shaped amphiphilic copolymer POSS-DP-CAG-TAT-NLS[94]. Reproduced with permission from copyright(2018) American Chemical Society.
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