Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis.

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region.

Macrophage-derived extracellular vesicles represent a promising endogenous iron-chelating therapy for iron overload and cardiac injury in myocardial infarction.

Background: Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts.

Targeted delivery of MerTK protein via cell membrane engineered nanoparticle enhances efferocytosis and attenuates atherosclerosis in diabetic ApoE Mice.

Background: Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis.

Results: In this study, we found that diabetic ApoE mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed.

Lipid overload-induced RTN3 activation leads to cardiac dysfunction by promoting lipid droplet biogenesis.

Lipid droplet (LD) accumulation is a notable feature of obesity-induced cardiomyopathy, while underlying mechanism remains poorly understood. Here we show that mice fed with high-fat diet (HFD) exhibited significantly increase in cardiac LD and RTN3 expression, accompanied by cardiac function impairment. Multiple loss- and gain-of function experiments indicate that RTN3 is critical to HFD-induced cardiac LD accumulation.

Targeted elimination of senescent cells by engineered extracellular vesicles attenuates atherosclerosis in ApoE mice with minimal side effects.

Senescent cells in plaques emerge as a detrimental factor for atherosclerosis (AS), for which targeted senolysis might be a promising therapeutic strategy. The development of safe and efficient senolytics for senescent cell eradication by targeted delivery is greatly needed. Pro-apoptotic intelligent (i)-overexpressing plasmid was constructed by molecular cloning, in which CDS was fused to miR-122 recognition sites.

Improved extracellular vesicle-based mRNA delivery for familial hypercholesterolemia treatment.

Extracellular vesicle (EV)-based low-density lipoprotein receptor () mRNA delivery showed excellent therapeutic effects in treating familial hypercholesterolemia (FH). Nevertheless, the loading inefficiency of EV-based mRNA delivery presents a significant challenge. Recently, RNA-binding proteins (RBPs) have been fused to EV membrane proteins for selectively encapsulating targeted RNAs to promote loading efficiency.

Ultrasound Responsive Nanovaccine Armed with Engineered Cancer Cell Membrane and RNA to Prevent Foreseeable Metastasis.

Cancer vaccine has been considered as a promising immunotherapy by inducing specific anti-tumor immune response. Rational vaccination at suitable time to efficiently present tumor associated antigen will boost tumor immunity and is badly needed. Here, a poly (lactic-co-glycolic acid) (PLGA)-based cancer vaccine of nanoscale is designed, in which engineered tumor cell membrane proteins, mRNAs, and sonosensitizer chlorin e6 (Ce6) are encapsulated at high efficiency.

Associations of human papillomavirus genotypes and cervical vascular abnormality in a cohort of women underwent colposcopy, a retrospective study of 6716 patients.

Aims: Abnormal vessel patterns are specific signs in patients with early cervical abnormality and cervical cancer(CC) by colposcopy, but the impact of human papillomavirus (HPV) infections on abnormal vessel patterns remains unknown.

Methods: A total of 6716 female patients with HPV infections or cytological abnormalities who underwent a colposcopy following abnormal CC screening results were included in the study. The final pathological diagnosis was confirmed to be the most severe pathological grade across cervical biopsy, endocervical canal curettage (ECC) and conization.

Exosome-Based Mitochondrial Delivery of circRNA mSCAR Alleviates Sepsis by Orchestrating Macrophage Activation.

Sepsis is one of the most common causes of death, which is closely related to the uncontrolled systemic inflammation. Dysregulation of M1 macrophage polarization is the primary contributor to serious inflammation. In this study, it is revealed that the murine homologue of circRNA SCAR (steatohepatitis-associated circRNA ATP5B regulator), denoted as circRNA mSCAR hereafter, decreases in the macrophages of septic mice, which correlates with the excessive M1 polarization.

"All-in-One" Exosome Engineering Strategy for Effective Therapy of Familial Hypercholesterolemia.

Exosomes serve as a promising therapeutic nanoplatform. However, the exosomes produced by donor cells are a heterogeneous group, with only a small portion having high therapeutic efficacy. Specific isolation of the subpopulation with high efficacy is important for lowering the dose and minimizing toxicity.

An optimized exosome production strategy for enhanced yield while without sacrificing cargo loading efficiency.

Background: Exosome mediated mRNA delivery is a promising strategy for the treatment of multiple diseases. However, the low yield of exosomes is a bottleneck for clinical translation. In this study, we boosted exosome production via simultaneously reducing the expression of genes inhibiting exosome biogenesis and supplementing the culture medium with red cell membrane components.

Early Assessment of Atherosclerotic Lesions and Vulnerable Plaques in vivo by Targeting Apoptotic Macrophages with AV Nanobubbles.

Background: The early detection of atherosclerotic lesions is particularly important for risk prediction of acute cardiovascular events. Macrophages apoptosis was significantly associated with the degree of AS lesions and especially contributed to plaque vulnerability. In this research, we mainly sought to explore the feasibility of a home-made AV-nanobubbles (NB) for visualization of apoptotic macrophages and assessment of atherosclerosis (AS) lesions by contrast-enhanced ultrasound (CEUS) imaging.

Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic mice.

Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout ( ) mice, in which increased expression of long-chain acyl-CoA synthetase 1 () in macrophages played an important role.

Exosome-mediated delivery of inflammation-responsive mRNA for controlled atherosclerosis treatment.

Tailored inflammation control is badly needed for the treatment of kinds of inflammatory diseases, such as atherosclerosis. IL-10 is a potent anti-inflammatory cytokine, while systemic and repeated delivery could cause detrimental side-effects due to immune repression. In this study, we have developed a nano-system to deliver inflammation-responsive mRNA preferentially into macrophages for tailored inflammation control.

Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension.

Arterial stiffness due to the vessel remodeling is closely linked to raised blood pressure, and its physiopathologic mechanism is still not fully understood. We here aimed to explore whether extracellular vesicle (EV) mediated intercellular communication between endothelium and smooth muscle cell contribute to the blood vessel remodeling under hypertension. We here revealed that the arterial endothelial cells robustly secreted EV, which in turn could be circulated and/or directly taken up by the subendothelial smooth muscle cells (SMC).

HIF1α epigenetically repressed macrophages via CRISPR/Cas9-EZH2 system for enhanced cancer immunotherapy.

Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer immunotherapy. In this study, we identified that HIF1 was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive microenvironment. Epigenetically silencing of via histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system, in which histone H3 methylase EZH2 was recruited to the promoter region specifically.

Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets.

Exosomes are nanosized lipid vesicles originating from the endosomal system that carry many macromolecules from their parental cells and play important roles in intercellular communication. The functions and underlying mechanisms of exosomes in atherosclerosis have recently been intensively studied. In this review, we briefly introduce exosome biology and then focus on advances in the roles of exosomes in atherosclerosis, specifically exosomal changes associated with atherosclerosis, their cellular origins and potential functional cargos, and their detailed impacts on recipient cells.

Maternal obesity increases the risk of fetal cardiac dysfunction via visceral adipose tissue derived exosomes.

Introduction: There is a strong association between gestational obesity and fetal cardiac dysfunction, while the exact mechanisms remain largely unknown. The purpose of this study was to investigate the role of exosomes from maternal visceral adipose tissue in abnormal embryonic development in obese pregnancy.

Methods: Female C57BL/6J obese mice were induced by a high-fat diet (containing 60% fat).

Exosome-based gene therapy for familial hypercholesterolemia in a mouse model.

Familial hypercholesterolemia (FH), with high LDL (low-density lipoprotein) cholesterol levels, is due to inherited mutations in genes, such as low-density lipoprotein receptor (LDLR). Development of therapeutic strategies for FH, which causes atherosclerosis and cardiovascular disease, is urgently needed. Mice with low-density lipoprotein receptor deletion ( mice) were used as an FH model.

Fusion protein engineered exosomes for targeted degradation of specific RNAs in lysosomes: a proof-of-concept study.

Therapeutically intervening the function of RNA in vivo remains a big challenge. We here developed an exosome-based strategy to deliver engineered RNA-binding protein for the purpose of recruiting specific RNA to the lysosomes for degradation. As a proof-of-principle study, RNA-binding protein HuR was fused to the C-terminus of Lamp2b, a membrane protein localized in both exosome and lysosome.

Ultrasound targeted microbubble destruction assisted exosomal delivery of miR-21 protects the heart from chemotherapy associated cardiotoxicity.

Chemotherapy related cardiotoxicity is now becoming one of the biggest hurdles for the prognosis of cancer patients. Therapeutically delivering protective small RNAs holds promise for the cardiotoxicity prevention and therapy. However, heart is intrinsically refractory to the nanoparticle-mediated drug delivery.

Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice.

The ever-increasing incidence of obesity and related disorders impose serious challenges on public health worldwide. Brown adipose tissue (BAT) has strong capacity for promoting energy expenditure and has shown great potential in treating obesity. Exosomes are nanovesicles that share the characteristics of their donor cells.

Visceral Adipose Tissue Derived Exosomes Exacerbate Colitis Severity Pro-inflammatory MiRNAs in High Fat Diet Fed Mice.

A pioneering epidemic study has revealed a strong association between obesity and the risk of colitis. In this study, a high fat diet was found to significantly aggravate colitis induced by dextran sulfate sodium (DSS). Meanwhile, a high fat diet changed the miRNA profile of the visceral adipose exosomes, switching the exosomes from anti-inflammatory to a pro-inflammatory phenotype.

Delivery Efficacy Differences of Intravenous and Intraperitoneal Injection of Exosomes: Perspectives from Tracking Dye Labeled and MiRNA Encapsulated Exosomes.

Background: Exosomes are cell-derived nanovesicles that play vital roles in intercellular communication. Recently, exosomes are recognized as promising drug delivery vehicles. Up till now, how the distribution of exosomes is affected by different administration routes has not been fully understood.