Construction Of Biomimetic Nanoparticles And Their Cardiac Repair Application

Exosomes derived from mesenchymal stem cells have shown great potential for the treatment of myocardial infarction.As one of the key components of exosome,micro RNA(miRNA)shows important therapeutic function.However,the major challenges of miRNA therapy remained in in vivo instability and low cellular transfection efficiency.To address above issues,encapsulation of mesenchymal stem cell membranes can confer nanoparticle with long circulation ability of blood and cardiomyocyte targeting ability,so as to realize the efficient delivery of miRNA and the effective recovery of cardiac function.This thesis focuses on a series of studies on the synthesis and performance of stem cell membrane camouflage nanocomposites and the protective behavior of the myocardium at the cellular and animal levels.The main research work is summarized as follows:In chapter 1,we summarized the progress of miRNA in the treatment of myocardial infarction and the development of cell membrane encapsulation technology,providing a theoretical basis for the research of this topic.In chapter 2,we used bone marrow mesenchymal stem cell membranes to encapsulate miR-loaded mesoporous silica nanoparticles to synthesize a new type of biomimetic nanocarrier(CM-miR-MSN).The material owns a core-shell structure with a particle size of 110 nm.Stem cell membrane of the surface was completely and retains related functional proteins.CM-miR-MSN can effectively adsorb miRNA and has good physiological stability and biocompatibility.By simulating the intracellular environment in vitro,it was verified that the miRNA can be released effectively.In chapter 3,we investigated the therapeutic effects of CM-miR-MSN in vitro.First,the targeted ability to cardiomyoytes and the escape from macrophage clearance were verified.Confocal microscopy was used to characterize the internalization of CM-miR-MSN by cardiomyocytes,which could successfully achieve lysosomal escape and miRNA release.The silence efficiency of the material to PDCD4 and PTEN is as high as about 70%.Finally,the protective effect on cardiomyocytes under hypoxic conditions was comprehensively evaluated by live-dead staining and apoptosis experiments.In chapter 4,we investigated the cardiac repair ability of CM-miR-MSN in vivo.The M-mode echocardiography measurements showed that CM-miR-MSN promoted the recovery on the cardiac pulsation after myocardial infarction.Masson staining and immunohistochemical proved that CM-miR-MSN can effectively reduce the infarct area and promote the proliferation of cardiomyocytes.At the same time,CM-miR-MSN was non-toxic on other organs.In the last chapter,we summarized and forecast the work of this thesis.The CM-miR-MSN synthesized in this work can achieve accurate and efficient delivery of miRNA,and can effectively recover heart function.It is expected to be used in tissue engineering,drug delivery,disease diagnosis and other related fields.