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

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Abstract

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.

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Data Availability

No datasets were generated or analysed during the current study.

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Acknowledgements

This research was funded by the Natural Science Foundation of China (grant number 3210120332), the Natural Science Foundation of Hebei Province (B2023201108), the Research and Innovation Team Project of Hebei University (IT2023B01) and the Post-graduate’s Innovation Fund Project of Hebei University (grant number HBU2023SS013).

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Authors and Affiliations

  1. College of Chemistry and Materials Science, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China

    Xueyu Fan, Shuangqing Fu, Shuo Wang, Shuo Ma, Jie Du, Wei Li & Honglei Zhang

  2. Department of Life Science, Hengshui University, Hengshui, 053000, China

    Chao Zhang

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  1. Xueyu Fan
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  7. Wei Li
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Contributions

Conceptualization: X.F., W.L., H.Z. and S.F.; methodology: X.F., C.Z., S.F., S.W., J.D. and S.M.; validation: X.F., C.Z., S.F., S.W., and S.M.; formal analysis: X.F., C.Z.; resources: J.D., W.L. and H.Z.; data curation: X.F. and S.F.; writing—original draft preparation: X.F.; writing—review and editing: X.F., J.D., W.L. and H.Z.; supervision: J.D., W.L. and H.Z.; funding acquisition: W.L. and H.Z. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jie Du, Wei Li or Honglei Zhang.

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Fan, X., Zhang, C., Fu, S. et al. In Situ Assembly of Melittin-PHA Microspheres for Enhancing Therapeutic Efficacy in Cancer Treatment. Int J Pept Res Ther 30, 30 (2024). https://doi.org/10.1007/s10989-024-10600-2

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