In Situ Assembly of Melittin-PHA Microspheres for Enhancing Therapeutic Efficacy in Cancer Treatment

Amphiphilic cationic peptide (ACP) is a widely studied biofilm-active peptide that has great potential in cancer treatment. However, poor stability, a short half-life, and complex preparation pose significant challenges for practical therapeutic applications. In the current investigation, the amphiphilic peptide Melittin (Mel), recognized for its powerful anticancer properties, was chosen from natural and synthetic ACP, and integrated into a nanostructure by utilizing polyhydroxyalkanoate (PHA) microspheres as carriers to produce Mel-loaded PHA microspheres (Mel@PHA-PhaC). Mel@PHA-PhaC nanostructure was self-assembled in Escherichia coli, simplifying its preparation and making it more convenient and high-yield. Mel@PHA-PhaC were spherical, with a particle size of approximately 300 nm, as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The concentration of Mel in Mel@PHA-PhaC was 4 μg/mg. Mel@PHA-PhaC still maintained good stability after being treated with pancreatic enzymes. Furthermore, in vitro experiments demonstrated that Mel@PHA-PhaC enhanced the inhibitory effect on cancer cells compared to free Mel. This study provides insights and guidelines for the development and utilization of peptide delivery systems using PHA microspheres to create stable and improved peptides for cancer therapy.