Bovine serum albumin-based biomimetic gene complexes with specificity facilitate rapid re-endothelialization for anti-restenosis

Re-endothelialization is a critical problem to inhibit postoperative restenosis, and gene delivery exhibits great potential in rapid endothelialization. Unfortunately, the therapeutic effect is enormously limited by inefficient specificity, poor biocompatibility and in vivo stability owing largely t...

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Bibliographic Details
Published in:Acta biomaterialia 2022-04, Vol.142, p.221-241
Main Authors: Hao, Xuefang, Gai, Weiwei, Ji, Feng, Zhao, Jiadi, Sun, Dandan, Yang, Fan, Jiang, Haixia, Feng, Yakai
Format: Article
Language:English
Subjects:
Animals
Anti-restenosis
Biocompatibility
Biological properties
Biomimetics
Bovine serum albumin
Carotid artery
Cattle
Cell Proliferation
Constriction, Pathologic - metabolism
Endothelial Cells
Endothelium
Endothelium, Vascular - metabolism
Gene complexes
Gene transfer
Homing behavior
Hyperplasia
Hyperplasia - pathology
In vivo methods and tests
Internalization
Mice
Neointima - metabolism
Platelet membrane
Platelets
Polyethyleneimine
Re-endothelialization
Restenosis
Serum albumin
Serum Albumin, Bovine - pharmacology
Stability
Stents
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
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Summary:Re-endothelialization is a critical problem to inhibit postoperative restenosis, and gene delivery exhibits great potential in rapid endothelialization. Unfortunately, the therapeutic effect is enormously limited by inefficient specificity, poor biocompatibility and in vivo stability owing largely to the complicated in vivo environment. Herein, we developed a series of platelet membrane (PM) cloaked gene complexes based on natural bovine serum albumin (BSA) and polyethyleneimine (PEI). The gene complexes aimed to accelerate re-endothelialization for anti-restenosis via pcDNA3.1-VEGF165 (VEGF) plasmid delivery. Based on BSA and PM coating, these gene complexes exhibited good biocompatibility, stability with serum and robust homing to endothelium-injured site inherited from platelets. Besides, they enhanced the expression of VEGF protein by their high internalization and nucleus accumulation efficiency, and also substantially promoted migration and proliferation of vascular endothelial cells. The biological properties were further optimized via altering PEI and PM content. Finally, rapid recovery of endothelium in a carotid artery injured mouse model (79% re-endothelialization compared with model group) was achieved through two weeks’ treatment by the PM cloaked gene complexes. High level of expressed VEGF in vivo was also realized by the gene complexes. Moreover, neointimal hyperplasia (IH) was significantly inhibited by the gene complexes according to in vivo study. The results verified the great potential of the PM cloaked gene complexes in re-endothelialization for anti-restenosis. Rapid re-endothelialization is a major challenge to inhibit postoperative restenosis. Herein, a series of biodegradable and biocompatible platelet membrane (PM) cloaked gene complexes were designed to accelerate re-endothelialization for anti-restenosis via pcDNA3.1-VEGF165 (VEGF) plasmid delivery. The PM cloaked gene complexes provided high VEGF expression in vascular endothelial cells (VECs), rapid migration and proliferation of VECs and robust homing to endothelium-injured site. In a carotid artery injured mouse model, PM cloaked gene complexes significantly promoted VEGF expression in vivo, accelerated re-endothelialization and inhibited neointimal hyperplasia due to their good biocompatibility and superior specificity. Overall, the optimized PM cloaked gene complexes overcomes multiple obstacles in gene delivery for re-endothelialization and can be a promising candidate f
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2022.02.005