Targeted delivery of a short antimicrobial peptide against CD44-overexpressing tumor cells using hyaluronic acid-coated chitosan nanoparticles: An in vitro study

摘要

Background Studies have shown that cationic antimicrobial peptides can be effective against tumor cells. Accordingly, in the current study, we evaluated the antitumor activity of a short cationic antimicrobial peptide (CM11) against CD44 overexpressing tumor cell lines, A549, SH-SY5Y, and PANC-1, by developing a targeted delivery system based on hyaluronic acid-coated chitosan nanoparticles (HA-CS NPs) in vitro. Methods For preparation of delivery system, CM11-loaded chitosan nanoparticles were fabricated by the ionic gelation method, and in order to bond the carboxylic group of hyaluronic acid to amine groups of chitosan, EDC as the coupling agent was used. Results Following the optimization, the particle size and zeta potential of HA-CS NPs were measured which were 190 nm and + 28.9 mv with reasonable PDI of 0.280. In addition, encapsulation efficiency of peptide in nanoparticles was estimated approximately 60%. The in vitro release rate of the peptide from nanoparticles was also pH-dependent, which was higher in acidic pH (5-6) compared with the physiological pH (7.4). Based on MTT assay, the cytotoxicity of CM11-loaded HA-CS NPs against tumor cell lines was significantly higher compared with the CM11-loaded CS NPs and free peptide, while the cytotoxic effect of the free peptide on the normal cells was more than the nanoparticles containing the peptide. Flow cytometry-based apoptosis/necrosis assay also exhibited CM11-NP-induced apoptotic cell death. Conclusion Our findings confirm the significant potential of CM11 peptide against tumor cells and its delivery system in order to target these cells.