Polydopamine Drug-loaded Nanoparticles Knotted Injectable Hydrogels To Treat Myocardial Infarction

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.A polydopamine drugloaded NPs 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 hydrophilic drug epigallocatechin-3-gallate(EGCG)throughπ-π interactions.The resulted drug-loaded NPs exhibited a “three-in-one” capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH.Polydopamine drug-loaded 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 dopamine drug-loaded 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(RT-PCR)demonstrated a downregulation of inflammatory factors(tumor necrosis factor-α,interleukin‐1β,interferonγ),up-regulation of vascular related growth factors(hypoxia inducible factor-1α,vascular endothelial growth factor A,von Willebrand factor,angiopoietin-1)and cardiac-related m RNAs(gap junction protein,Cadherin 2).All in all,in this thesis,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting polydopamine drug-loaded NPs knotted hydrogels is developed.This method can reverse hostile microenvironment,with an ability to scavenge ROS,down-regulate pro-inflammation factors in the first stage,and promote anagenesis in a long term,thereby contributing to a significant improvement of heart functions.