Hyaluronic Acid-Coated Bovine Milk Exosomes for Achieving Tumor-Specific Intracellular Delivery of miRNA-204

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 19; p. 3065
• Main Authors: Li, Dan, Gong, Liang, Lin, Han, Yao, Surui, Yin, Yuan, Zhou, Zhifang, Shi, Jie, Wu, Zhimeng, Huang, Zhaohui
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 29.09.2022; MDPI
• Subjects: Antitumor activity; Biocompatibility; Cancer; Cancer therapies; Care and treatment; CD44; CD44 antigen; Cell differentiation; Cell organelles; Chemotherapy; Cow's milk; Drug delivery; Drug delivery systems; Drugs; Efficiency; Exosomes; Health aspects; Hyaluronic acid; Intracellular; Laboratory animals; Ligands; MicroRNA; MicroRNAs; milk exosomes; miRNA; Morphology; Nanoparticles; Polyclonal antibodies; Targeted cancer therapy; Toxicity; Tumor cells; tumor-specific delivery; China; United Kingdom > UK; United States > US
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11193065

Cell type-specific drug delivery is a straightforward strategy to achieve targeted cancer therapy and reduce side effects. Hyaluronic acid (HA), an U.S. Food and Drug Administration (FDA)-approved biocompatible carbohydrate polymer, has been extensively employed as a targeting ligand for a drug delivery system due to its natural ability to bind to tumor cells overexpressing cluster of differentiation 44 (CD44) receptors. Here, we report the preparation and antitumor efficacy of HA-coated bovine milk exosomes (HA-mExo) for tumor-specific delivery of microRNA-204-5p mimics (miR-204). The exosome-based delivery formulation was prepared with miR-204 encapsulated inside the lumen and HA displayed outside the membrane. The resultant formulation of HA-mExo-miR204 was able to specifically target CD44-positive cancer cells, with a concomitant increase in the intracellular uptake of miR-204. Compared to the uncoated mExo-miR204 formulation, HA-mExo-miR204 showed significantly increased antitumor efficacy both in vitro and in vivo. Importantly, HA-mExo-miR204 showed excellent biocompatibility and did not cause significant systemic toxicity. Given that both HA and bovine milk exosomes are low-cost and highly accessible biogenic materials with broad biomedical applications, HA-decorated bovine milk exosomes can be proven to be a practical drug delivery system of RNA drugs for targeted cancer therapy.