Abstract
Over the years, there has been a high demand for developing new safe and effective drug carriers for cancer therapy. Emerging studies have indicated that exosomes can serve as potent therapeutic carriers since they offer low immunogenicity, high stability, innate and acquired targetability, and the stimulation of anti-cancer immune responses. Yet, the development of exosome-based drug delivery systems remains challenging due to their heterogeneity, low yield, and limited drug loading efficiency. Herein, we summarized the current application of exosomes derived from different cells as drug carriers in anti-cancer therapy in vitro and in vivo. We also discussed the challenges and prospects of exosome-based drug delivery systems in cancer therapy.
Highlights
Compared to liposomes and nanoparticles, exosomes have the following advantages: 1) low immunogenicity; 2) low clearance of reticuloendothelial system in vivo; 3) higher bioavailability; 4) low accumulative toxicity in normal tissues; 5) selectively delivering anti-cancer drugs into cancer cells via ligand-receptor interaction or endocytosis to overcome drug resistance mediated by P-glycoprotein or other multidrug resistance-associated proteins (Kim et al, 2016); 6) the plasticity of acquired targetability to cancer cells; 7) the stimulation of anti-tumor immune responses
Jong et al found that mouse bone marrow Mesenchymal stem cells (MSCs)–derived exosomes reduced vascular endothelial growth factor (VEGF) expression in breast cancer to inhibit angiogenesis in tumor tissues, thereby suppressing tumor growth in mice with breast cancer (Lee et al, 2013)
Hosna et al demonstrated that engineered MSCs with lysosomeassociated membrane glycoprotein 2 (LAMP2)-Designed ankyrin repeat protein (DARPin) could produce exosomes rich in LAMP2-DARPin
Summary
Cancer is a major public health problem and a leading cause of death worldwide. In 2020, 19.3 million new cancer cases and approximately 10.0 million cancer-related deaths were reported (Sung et al, 2021). Numerous synthetic drug carriers, such as liposomes and nanoparticles, have been developed to cure cancer (Perez-Herrero and Fernandez-Medarde, 2015) These carries can either passively or actively target cancerous cells, reducing adverse side effects and improving. Compared to liposomes and nanoparticles, exosomes have the following advantages: 1) low immunogenicity; 2) low clearance of reticuloendothelial system in vivo; 3) higher bioavailability (can pass through biological barriers, including intestinal barrier, blood-brain barrier, and placental barrier); 4) low accumulative toxicity in normal tissues; 5) selectively delivering anti-cancer drugs into cancer cells via ligand-receptor interaction or endocytosis to overcome drug resistance mediated by P-glycoprotein or other multidrug resistance-associated proteins (Kim et al, 2016); 6) the plasticity of acquired targetability to cancer cells; 7) the stimulation of anti-tumor immune responses. This review discussed the application, challenges, and prospects of exosome-based drug delivery systems in cancer therapy
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