An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium

Yang, Huaxiao1; Qin, Xulei1; Wang, Huiyuan2; Zhao, Xin1; Liu, Yonggang1; Wo, Hung-Ta1; Liu, Chun1; Nishiga, Masataka1; Chen, Haodong1; Ge, Jing3; Sayed, Nazish1; Abilez, Oscar J.1; Ding, Dan4; Heilshorn, Sarah C.2; Li, Kai3,5

2019-09

10.1021/acsnano.9b03343

ACS Nano   影响因子和分区

1936-0851

1936-086X

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.

cardiovascular disease regenerative medicine gene delivery conjugated polymer myocardial infarction

SCI ; EI

英语

NI期刊

通讯

National Institutes of Health[R21 HL138042] ; National Institutes of Health[R01 HL 142718] ; National Institutes of Health[K01 HL130608]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000487859600011

AMER CHEMICAL SOC

20192507073777

Cardiology ; Conjugated polymers ; Endothelial cells ; Gene transfer ; Hydrogels ; Liposomes ; Regenerative Medicine ; Restoration ; Shear thinning ; Stem cells

Bioengineering and Biology:461 ; Fluid Flow, General:631.1 ; Chemical Products Generally:804 ; Organic Polymers:815.1.1

Web of Science

1.Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA
2.Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA
3.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Guangdong, Peoples R China
4.Nankai Univ, State Key Lab Med Chem Biol, Key Lab Bioact Mat, Minist Educ,Coll Life Sci, Tianjin 300071, Peoples R China
5.Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA

Yang, Huaxiao,Qin, Xulei,Wang, Huiyuan,et al. An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium[J]. ACS Nano,2019,13(9):9880-9894.

Yang, Huaxiao.,Qin, Xulei.,Wang, Huiyuan.,Zhao, Xin.,Liu, Yonggang.,...&Li, Kai.(2019).An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium.ACS Nano,13(9),9880-9894.

Yang, Huaxiao,et al."An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium".ACS Nano 13.9(2019):9880-9894.