“Ferrero-like”nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts  

作　　者：HAN XiaoXu LI Lan XIE Tian CHEN Si ZOU Yang JIN Xin LI Sheng WANG Meng HAN Ning FAN GuanWei LIU WenGuang WANG Wei 

机构地区：[1]School of Materials Science and Engineering,Tianjin Key Laboratory of Composite and Functional Materials,Tianjin University,Tianjin 300072,China [2]First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China [3]Tianjin State Key Laboratory of Modern Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China

出　　处：《Science China(Technological Sciences)》2020年第11期2435-2448,共14页中国科学（技术科学英文版）

基　　金：This work was supported by the Excellent Young Scientists Fund by National Natural Science Foundation of China(Grant No.31822020);the National Natural Science Foundation of China(Grant Nos.31771030&31870965);the National Key Research and Development Program of China(Grant No.2016YFC1101301);and Tianjin Outstanding Youth Science Foundation(Grant No.17JCJQJC46200).

摘　　要：Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a permanently inadequate blood supply.Herein,an injectable hydrogel fabricated by nanoparticles(NPs)knotted thiolated hyaluronic acid(HA-SH)was reported to reverse the hostile microenvironment and rebuild the heart functions after MI.Inspired by the composite shell-core structure of Ferrero chocolate sphere,a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine(DMOG)NPs core and a thick polydopamine(PDA)shell formed by the self-polymerization of dopamine embedded with watersoluble drug epigallocatechin-3-gallate(EGCG)throughπ-πinteractions.The resulted"Ferrero-like"NPs exhibited a"three-inone"capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH."Ferrero-like"NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property,high capability to capture ROS,and programmed release of EGCG and DMOG.Four weeks after deploying the"Ferrero-like"NPs knotted hydrogels into rat infarcted hearts,the ejection fraction(EF)increased by 23.7%,and the infarct size decreased by 21.1%,and the fibrotic area reduced by 24.4%.The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction(RTPCR)demonstrated a down-regulation of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)),up-regulation of vascular related growth factors(hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),von Willebrand factor(vWF),angiopoietin-1(Ang-1))and cardiac-related m RNAs(gap junction protein(Cx43),Cadherin 2).All in all,in this report,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting"Ferrero-like"NPs knotted hydrogels is developed to reverse hostile microenvironmen

关 键 词：myocardial infarction injectable hydrogel reactive oxygen species epigallocatechin-3-gallate dimethyloxalylglycine 

分 类 号：R542.22[医药卫生—心血管疾病] R318.08[医药卫生—内科学]