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Functional Nanocomplexes with Vascular Endothelial Growth Factor A/C Isoforms Improve Collateral Circulation and Cardiac Function
Author(s) -
Qiao Bokang,
Nie JingJun,
Shao Yihui,
Li Yulin,
Zhang Congcong,
Hao Wenjing,
Li Sijin,
Chen Dafu,
Yu Bingran,
Li HuiHua,
Xu FuJian,
Du Jie
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201905925
Subject(s) - angiogenesis , vascular endothelial growth factor , heparin , cardiac function curve , pharmacology , cancer research , myocardial infarction , medicine , chemistry , vegf receptors , heart failure
Protein‐based therapies are potential treatments for cancer, immunological, and cardiovascular diseases. However, effective delivery systems are needed because of their instability, immunogenicity, and so on. Crosslinked negatively charged heparin polysaccharide nanoparticle (HepNP) is proposed for protein delivery. HepNP can efficiently condense vascular endothelial growth factor (VEGF) because of the unique electronegative sulfonic acid and carboxyl domain of heparin. HepNP is then assembled with VEGF‐C (Hep@VEGF‐C) or VEGF‐A (Hep@VEGF‐A) protein for the therapy of myocardial infarction (MI) via intravenous (iv) injection. Hep@VEGF‐A‐mediated improvement of cardiac function by promoting angiogenesis is limited because of elevated vascular permeability, while Hep@VEGF‐C effectively promotes lymphangiogenesis and reduces edema. On this basis, a graded delivery of VEGF‐C (0.5–1 h post‐MI) and VEGF‐A (5 d post‐MI) using HepNP is developed. At the dose ratio of 3:1 (Hep@VEGF‐C vs Hep@VEGF‐A), Hep@VEGF functional complexes substantially reduce the scar formation (≈−39%; p < 0.05) and improve cardiac function (≈+74%; p < 0.05). Such a HepNP delivery system provides a simple and effective therapeutic strategy for cardiovascular diseases by delivering functional proteins. Because of the unique binding ability of heparin with cytokines and growth factors, HepNP also has considerable application prospects in protein therapy for other serious diseases.