Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis

Thapa, Narendra; Hong, Hai Yan; Purushotham, Sangeetha; Kim, In San; Yoo, Jeongsoo; Rhee, Kyehan; Oh, Goo Taeg; Kwon, Ick Chan; Lee, Byung Heon

doi:10.1016/j.jconrel.2008.07.013

Cited by 24 publications

(10 citation statements)

References 30 publications

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“…Rabies viral glycoprotein peptide (YTIWMPENPRPGTPCDIFTNSRGKRASNG) displayed on the external part of exosomes can specifically bind to acetylcholine receptor 39. In terms of the cardiovascular system, several homing peptides have been identified and applied to targeted therapy, including atherosclerosis,40, 41, 42 pulmonary arterial hypertension,43 and ischemia/reperfusion injured cardiomyocytes 44. In research by Won et al,44 they presented that a polymeric gene carrier conjugated with IMTP (CSTSMLKAC) was capable of targeting ischemic myocardium, resulting in high localization within the ischemic zone of the LV of an ischemia/reperfusion rat model on systemic administration.…”

Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

290

206

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BackgroundExosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium.Methods and ResultsWe used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area.ConclusionsOur research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

290

206

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“…Both targeted and untargeted exosomes accumulated in the liver, however, indicating that targeting did not prevent off-target delivery. Peptides targeting unknown receptors on intended tissues have also been identified (Lee et al 2015;Thapa et al 2008).…”

Section: Targeted Exosomesmentioning

confidence: 99%

Exosomes: Therapy delivery tools and biomarkers of diseases

Barile

Vassalli

2017

Pharmacology & Therapeutics

870

619

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Virtually all cells in the organism secrete extracellular vesicles (EVs), a heterogeneous population of lipid bilayer membrane-enclosed vesicles that transport and deliver payloads of proteins and nucleic acids to recipient cells, thus playing central roles in cell-cell communications. Exosomes, nanosized EVs of endosomal origin, regulate many pathophysiological processes including immune responses and inflammation, tumour growth, and infection. Healthy subjects and patients with different diseases release exosomes with different RNA and protein contents into the circulation, which can be measured as biomarkers. The discovery of exosomes as natural carriers of functional small RNA and proteins has raised great interest in the drug delivery field, as it may be possible to harness these vesicles for therapeutic delivery of miRNA, siRNA, mRNA, lncRNA, peptides, and synthetic drugs. However, systemically delivered exosomes accumulate in liver, kidney, and spleen. Targeted exosomes can be obtained by displaying targeting molecules, such as peptides or antibody fragments recognizing target antigens, on the outer surface of exosomes. Display of glycosylphosphatidylinositol (GPI)-anchored nanobodies on EVs is a novel technique that enables EV display of a variety of proteins including antibodies, reporter proteins, and signaling molecules. However, naturally secreted exosomes show limited pharmaceutical acceptability. Engineered exosome mimetics that incorporate desirable components of natural exosomes into synthetic liposomes or nanoparticles, and are assembled using controllable procedures may be more acceptable pharmaceutically. In this communication, we review the current understanding of physiological and pathophysiological roles of exosomes, their potential applications as diagnostic markers, and current efforts to develop improved exosome-based drug delivery systems.

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“…343 Using panning against cell lines of various types, such as fibroblasts and myoblasts, 368 peptides with high cellular specificity can be identified. In this manner, peptides have been isolated that have specificity for endothelial cells associated with atherosclerosis, 369 breast cancer cells, 370 hepatocellular carcinoma cells, 371 melanoma cells, 372 and ovarian cells, 373 among others. Ex vivo panning works similarly, except the library is screened against cells or tumor masses that have been isolated, and binding peptides have been identified for a range of cell types that include neuroblastoma cells, 374 islet cells, 375 and colonic adenoma cells.…”

Section: Applications Of Virus-based Particlesmentioning

confidence: 99%

Design of virus-based nanomaterials for medicine, biotechnology, and energy

2016

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Virus-based nanomaterials are versatile materials that naturally self-assemble and have relevance for a broad range of applications including medicine, biotechnology, and energy. This review provides an overview of recent developments in “chemical virology.” Viruses, as materials, provide unique nanoscale scaffolds that have relevance in chemical biology and nanotechnology, with diverse areas of applications. Some fundamental advantages of viruses, compared to synthetically programmed materials, include the highly precise spatial arrangement of their subunits into a diverse array of shapes and sizes and many available avenues for easy and reproducible modification. Here, we will first survey the broad distribution of viruses and various methods for producing virus-based nanoparticles, as well as engineering principles used to impart new functionalities. We will then examine the broad range of applications and implications of virus-based materials, focusing on the medical, biotechnology, and energy sectors. We anticipate that this field will continue to evolve and grow, with exciting new possibilities stemming from advancements in the rational design of virus-based nanomaterials.

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Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis

Cited by 24 publications

References 30 publications

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Exosomes: Therapy delivery tools and biomarkers of diseases

Design of virus-based nanomaterials for medicine, biotechnology, and energy

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