Folate-grafted glycyl-glycine-melphalan conjugate self-assembled amphilphilc nanomicelles augmented drug delivery, cytotoxicity and cellular uptake in human ovarian cancer cells

Abstract

Objectives

Folic acid was coupled to melphalan using glycyl-glycine (FA-Gly-Gly-Melphalan) to synthesise self-assembled nanomicelles for targeting ovarian cancer cells, SKOV3.

Methods and results

FA-Gly-Gly-Melphalan self-assembled nanomicelles were prepared with critical micellar concentration (CMC) of 12-μg/ml. The mean particle size of FA-Gly-Gly-Melphalan self-assembled nanomicelles was measured to be 95.9 ± 3.4-nm significantly (p < 0.05) higher than 73.8 ± 6.3-nm of Gly-Gly-Melphalan self-assembled nanomicelles. Subsequently, zeta-potential of FA-Gly-Gly-Melphalan self-assembled nanomicelles was estimated to be −28.0 ± 1.5-mV significantly (p < 0.05) lower than −36.6 ± 2.7-mV of Gly-Gly-Melphalan self-assembled nanomicelles. The IC₅₀ of FA-Gly-Gly-Melphalan self-assembled nanomicelles was estimated to be 4.1-μg/ml significantly (p < 0.001) lower than 14.2-μg/ml of Gly-Gly-Melphalan self-assembled nanomicelles and >18-μg/ml of melphalan. FA-Gly-Gly-Melphalan self-assembled nanomicelles preferentially accumulated in cytoplasm of SKOV3 cells nearby nucleus via receptor mediated endocytosis pathway after 24-h of incubation period, whilst Gly-Gly-Melphalan self-assembled nanomicelles were not incorporated sufficiently.

Conclusion

FA-Gly-Gly-Melphalan self-assembled nanomicelles warrant in depth in vivo study for their safety, efficacy, and potency in clinical settings.

Keywords:

• Ovarian cancer
• melphalan
• self-assembled nanomicelles
• cytotoxicity
• cellular uptake

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.