Extracellular vesicles (EVs) are secreted membrane-enclosed nano-sized particles (40-1,000 nm) that deliver biological information between cells. The molecular composition of these subcellular particles includes growth factor receptors, ligands adhesion proteins, mRNA, miRNAs, lncRNA and lipids that are derived from donor cells. A number of studies demonstrated that stem cell-derived EVs are the key mediator of tissue repair and regeneration in multiple animal disease models. In addition, the composition of these particles is known to be altered in cancer and disease pathology suggesting them for useful in diagnostic and therapeutic purposes. Their endogenous origin and biological properties offer benefits over conventional drug delivery systems (DDS), such as liposome, synthetic nanoparticles and prompted the further application of EVs as drug delivery vehicles for chemical drugs, genetic materials and proteins. The contents of EVs can be efficiently modified by chemical, biological or physical means. Thus, EVs can be an innovative DDS as it can overcome physical and biological barriers and safely deliver therapeutic drugs to target tissues. In this minireview, we summarized current progress on the strategies of drug loading onto EVs; and loading.

Aberrant vascular smooth muscle cell (VSMC) proliferation and migration are a major pathological phenomenon in vascular disease characterized by intimal thickening. The important role of the mammalian target of rapamycin (mTOR) signaling in VSMC proliferation has been previously reported. Consequently, down-regulation of mTOR pathway may be an effective way of controlling excessive VSMC proliferation. Since microRNAs (miRNA) are newly emerging regulators of virtually all the biological processes including cellular proliferation, miRNAs targeting mTOR pathway may be utilized to suppress aberrant VSMC proliferation during pathologic conditions. Thus, in the present study, we screened miRNAs targeting mTOR, and we identified miR-761 as a new mTOR targeting miRNA. Luciferase assay using luciferase vector containing 3'UTR of mTOR indicated that miR-761 directly targets mTOR mRNA leading to suppression of mTOR protein expression. Our data also indicate that miR-761 expression decreases during angiotensin II (AngII)-induced proliferation of VSMCs, and exogenous miR-761 delivery effectively inhibit the AngII-induced VSMC proliferation. Additionally, the results of migration tests demonstrate that down-regulation of mTOR using exogenous miR-761 suppresses AngII-induced migration of VSMCs as well. Taken together, the present study provided evidence that miR-761 can be a potent anti-proliferative agent for vascular diseases such as atherosclerosis and restenosis, and warrants further studies to validate the effectiveness of miR-761 in vivo.

No abstract