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A strategy for combating melanoma with oncogenic c-Myc inhibitors and targeted nanotherapy.

AIMS
The activity of the transcription factor c-Myc is dependent upon heterodimerization with Max to control target gene transcription. Small-molecule inhibitors of c-Myc-Max have exhibited low potency and poor water solubility and are therefore unsuitable for in vivo application. We hypothesized that a nanomedicine approach incorporating a cryptic c-Myc inhibitor prodrug could be delivered and enzymatically released in order to effectively inhibit melanoma.


MATERIALS & METHODS
An Sn-2 lipase-labile Myc inhibitor prodrug was synthesized and included in two αvβ3-targeted nanoparticle platforms (20 and 200 nm). The inherent antiproliferate potency was compared with the lipid-free compound using human and mouse melanoma cell lines.


RESULTS & CONCLUSION
These data demonstrate for the first time a successful nanodelivery of c-Myc inhibitors and their potential use to prevent melanoma.