CAGW and TAT‐NLS peptides functionalized multitargeting gene delivery system with high transfection efficiency

Abstract

Gene therapy has attracted much attention in vascular tissue engineering. However, it is still challenging to develop a novel gene carrier with multifunction to overcome the barriers in gene delivery. Herein, the multitargeting gene complexes were developed based on methoxy‐poly(ethylene glycol)‐b‐poly‐(D,L‐lactide‐co‐glycolide) (mPEG‐b‐PLGA), poly(d,l‐lactide‐co‐glycolide)‐g‐polyethylenimine‐g‐CAGW (PLGA‐g‐PEI‐g‐CAGW), cell‐penetrating peptide YGRKKRRQRRR (TAT), nuclear localization signals (NLS), and pEGFP‐ZNF580 (pDNA) with the purpose of enhancing the transfection of endothelial cells (ECs). The low cytotoxic multitargeting gene complexes could be easily prepared by adjusting the weight ratio of mPEG‐b‐PLGA and PLGA‐g‐PEI‐g‐CAGW. Meanwhile, CAGW peptide with selectively ECs‐targeting ability and TAT‐NLS peptide sequence with both cell‐penetrating ability and nuclear targeting capacity were simultaneously introduced into gene complexes in order to enable them with the multitargeting function so as to improve their gene delivery capacity. The pDNA loading capacity of these gene complexes was confirmed by agarose gel electrophoresis assay. MTT results demonstrated that the relatively cell viability of the multitargeting gene complexes was higher than those of other groups. These multitargeting gene complexes showed higher internalization and transfection efficiencies than other groups. These results revealed that CAGW and TAT‐NLS peptide sequences benefited for efficient gene delivery. Furthermore, the wound healing assay demonstrated that the multitargeting gene complexes could promote the proliferation and migration of ECs. These results collectively demonstrated that CAGW and TAT‐NLS peptides functionalized gene delivery system could effectively enhance the transfection of ECs, which has great potential in vascular tissue engineering.

Bioreducible cationic random copolymer for gene delivery

“…This carrier shows high cellular uptake (99%) and endosomal escape, but the nucleus accumulation of Cy5‐oligonucleotide is relatively low. The nuclear localization sequence peptides can enhance the nucleus accumulation 18,22,23 . Thus CBA‐AEP‐His can be modified by nuclear localization sequence peptides to further improve its transfection efficiency in future research.…”

“…Cationic polymers as non‐viral vectors have gained much attention in the field of gene delivery owing to their plenty of advantages over viral gene carriers, such as low immunogenicity, no incorporation of exogeneous gene into host chromosome, and modifiable multifunction for efficient gene delivery 6‐8 . Many cationic polymers, such as poly(L‐Lysine) (pLL), 9 poly(ethylene imine) (PEI), 10 polyphosphoesters, 11 cationic polycarbonate, 12 polyhedral oligomeric silsesquioxane (POSS), 13‐15 and peptides containing polymers have been investigated as non‐viral vectors 16‐18 . Among these cationic polymers, both branched PEI and linear PEI served as most efficient gene carriers in vitro and in vivo.…”

Polyethylenimine-modified graphene quantum dots promote endothelial cell proliferation

“…With the deepening of cardiovascular disease research, vascular endothelial growth factor (VEGF) [ 15 ], angiopoietin (Ang) [ 16 ], fibroblast growth factor (FGF) [ 17 ] and zinc-finger nuclear transcription factor gene (ZNF580) [ 18 ] have been found to promote the proliferation and migration of HUVECs. Among them, ZNF580 gene overexpression not only significantly enhanced HUVEC migration and proliferation [ 19 ], but also inhibited smooth muscle cell proliferation [ 20 ] and promoted endothelial progenitor cell differentiation to HUVECs [ 21 ], and enhanced angiogenesis through the eNOS/NO pathway [ 22 ].…”