Extracellular vesicles: Natural liver‐accumulating drug delivery vehicles for the treatment of liver diseases

Abstract

Extracellular vesicles (EVs) are excellent potential vectors for the delivery of therapeutic drugs. However, issues with biological safety and disease targeting substantially limit their clinical application. EVs from red blood cells (RBC‐EVs) are potential drug delivery vehicles because of their unique biological safety. Here, we demonstrated that EVs, including RBC‐EVs, show natural liver accumulation. Mechanistically, the liver environment induces macrophages to phagocytize RBC‐EVs in a C1q‐dependent manner. RBC‐EVs loaded with antisense oligonucleotides of microRNA‐155 showed macrophage‐dependent protective effects against acute liver failure (ALF) in a mouse model. These RBC‐EVs were also effective in treatment of ALF. Furthermore, compared to routine doses of doxorubicin and sorafenib (SRF), RBC‐EVs loaded with doxorubicin or SRF showed enhanced therapeutic effects on a murine model of orthotopic liver cancer through a mechanism dependent on macrophages. Importantly, drug‐loaded RBC‐EVs showed no systemic toxicity at therapeutically effective doses, whereas routine doses of doxorubicin and SRF showed obvious toxicity. Thus, drug‐loaded RBC‐EVs hold high potential for clinical applications in the treatment of liver disease therapy.

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

“…Extracellular vesicles (EVs) and nanovesicles (NVs) have recently been shown to have potential applications as drug carriers and may be used to overcome the limitations of cellrelated treatments (5,6,(17)(18)(19). Previous studies have shown that M1 macrophage-derived nanovesicles (M1NVs) inhibit tumor development and enhance the anti-tumor effects of programmed cell death ligand 1 (5).…”

Tumor‐derived exosomal BCYRN1 activates WNT5A/VEGF‐C/VEGFR3 feedforward loop to drive lymphatic metastasis of bladder cancer

“…Exosomes served as a nanometer biological microvesicle in transmitting various biomolecule have been characterized as a promising therapeutic target for human diseases 49–51 . Relevant studies have demonstrated the effectiveness achieved by targeting exosomal lncRNA to improve the immunotherapy and treat the metastatic peritoneal cancer, suggesting the wide application prospects of exosomal lncRNA in the treatment of tumors 52 .…”

“…Exosomes served as a nanometer biological microvesicle in transmitting various biomolecule have been characterized as a promising therapeutic target for human diseases. 49 , 50 , 51 Relevant studies have demonstrated the effectiveness achieved by targeting exosomal lncRNA to improve the immunotherapy and treat the metastatic peritoneal cancer, suggesting the wide application prospects of exosomal lncRNA in the treatment of tumors. 52 Here, we revealed that high level of BCYRN1 in urinary‐EXO from BCa patients was associated with the LN metastasis and poor prognosis of patients, providing the clinical evidence for targeting exosomal BCYRN1 to treat LN metastatic BCa.…”

Small extracellular vesicles from menstrual blood-derived mesenchymal stem cells (MenSCs) as a novel therapeutic impetus in regenerative medicine

“…Small EVs have a series of advantages as drug carriers, such as unique structure and physicochemical properties, effective cell access, low immunogenicity and toxicity, and natural capacity to cross organism barriers [ 198 , 199 ]. Additionally, MSC-derived small EVs can deliver drugs to recipient cells in a highly selective manner [ 98 , 200 ]. In other words, MSC-derived small EVs are an ideal delivery system for small molecular drugs.…”