期刊
ACS NANO
卷 13, 期 9, 页码 9880-9894出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b03343
关键词
cardiovascular disease; regenerative medicine; gene delivery; conjugated polymer; myocardial infarction
类别
资金
- Thousand Young Talents Program
- National Natural Science Foundation of China [31870991]
- American Heart Association (AHA) Postdoctoral Fellowship Award [18POST34030106, 17SDG33460212]
- National Institutes of Health [R21 HL138042, R01 HL 142718, K01 HL130608]
- Stanford Cardiovascular Institute (CVI)/Gooter Foundation seed grant
A major challenge in myocardial infarction (MI)-related heart failure treatment using microRNA is the efficient and sustainable delivery of miRNAs into myocardium to achieve functional improvement through stimulation of intrinsic myocardial restoration. In this study, we established an in vivo delivery system using polymeric nanoparticles to carry miRNA (miNPs) for localized delivery within a shear-thinning injectable hydrogel. The miNPs triggered proliferation of human embryonic stem cell-derived cardiomyocytes and endothelial cells (hESC-CMs and hESC-ECs) and promoted angiogenesis in hypoxic conditions, showing significantly lower cytotoxicity than Lipofectamine. Furthermore, one injected dose of hydrogel/miNP in MI rats demonstrated significantly improved cardiac functions: increased ejection fraction from 45% to 64%, reduced scar size from 20% to 10%, and doubled capillary density in the border zone compared to the control group at 4 weeks. As such, our results indicate that this injectable hydrogel/miNP composite can deliver miRNA to restore injured myocardium efficiently and safely.
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