A Strategy for Combating Melanoma with Oncogenic c-Myc Inhibitors and Targeted Nanotherapy

Abstract

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 α_vβ₃-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.

Keywords::

• c-Myc inhibitor
• melanoma
• nanotherapy
• prodrug

Financial & competing interests disclosure

The financial support from the American Heart Association (AHA) (0835426N and 11IRG5690011), NIH (under the grants NS059302, CA119342, CA1547371, NS073457 and HL073646) and the National Cancer Institute (NCI; under the grant N01CO37007) is greatly appreciated. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The financial support from the American Heart Association (AHA) (0835426N and 11IRG5690011), National Institute of Health NIH (under the grants NS059302, CA119342, CA1547371, NS073457 and HL073646) and the National Cancer Institute (NCI; under the grant N01CO37007) is greatly appreciated. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.