Anti-cancer effect of melittin-Au25(MHA)18 complexes on human cervical cancer HeLa cells

Melittin (MEL) is the major component of bee venom, which has recently emerged as an attractive candidate for cancer chemotherapy. As a polypeptide, rapid degradation of MEL is considered as one of the most critical challenges in therapeutic applications. In this study, atomically precise gold nanoclusters with 6-mercaptohexanoic acid (MHA) as a thiolate ligand, termed as Au25(MHA)18, were synthesized and employed as the delivery vehicles of MEL to human cervical cancer HeLa cells. The characterization including Zeta potential, UV–Vis spectra, X-ray photoelectron spectroscopy (XPS), and transmission electron microscope (TEM), showed that Au25(MHA)18 nanoclusters can load MEL with high efficiency, resulting in formation of MEL-Au25(MHA)18 complexes. The anti-cancer effect of MEL-Au25(MHA)18 complexes on human cervical cancer HeLa cells in vitro were further evaluated by cell proliferation and cytotoxicity assay, flow cytometry assay, and confocal microscopy imaging. It was found that Au25(MHA)18 nanoclusters protected MEL from degradation leading to long-lasting cytotoxicity on HeLa cells, and maintained the good anti-cancer activity of MEL. The anti-cancer activity of MEL-Au25(MHA)18 complexes on HeLa cells can be well explained through the pore formation by MEL on the surface of cell membrane, which ultimately leading to cytolysis. This work demonstrated the feasibility of atomically precise gold nanoclusters as the delivery vehicles of unstable polypeptide such as MEL, achieving improved efficiency in chemotherapy.