Developing nanoparticles to repurpose disulfiram as a treatment for skin cancers

Authors

• FS Davis
• SA Dixon
• A Chowdhury
• AM Krenek
• NL Sala
• L Mabundo
• ST Chung

Abstract

Merkel cell carcinoma (MCC) and acral lentiginous melanoma (ALM) are rare and aggressive skin cancers often treated with immunotherapy. Unfortunately, immunotherapy is not effective or appropriate for all patients, therefore new therapeutic options are needed. Using a high-throughput drug screen, we identified the aldehyde dehydrogenase inhibitor disulfiram (DSF) as an agent that selectively reduced MCC viability. DSF is known to kill other cancer lines and complexing it with copper (Cu) increases its anti-cancer activity. We discovered that combined DSF/Cu decreased the viability of MCC and ALM cell lines in vitro. However, DSF has poor pharmacokinetics and biodistribution in mice, hindering in vivo testing. To improve the in vivo stability and biodistribution of DSF, we created two nanoparticle (NP) formulations of DSF/Cu, a metal-organic framework (MOF) NP and a poly(lactic-co-glycolic acid) (PLGA) NP. MOF NP decreased cell viability in four MCC cell lines. PLGA NP decreased cell viability in four MCC and three ALM cell lines. As PLGA NP are more potent than MOF NP, we are testing these in xenograft mouse models of MCC and ALM. PLGA NP also reduced the viability of mouse melanoma B16F10 cells in vitro, which allows us to test the combined effect of NP plus immunotherapy in a mouse cancer model. Overall, we successfully developed a DSF/Cu PLGA NP formulation capable of decreasing cell viability in MCC, ALM, and mouse melanoma. Ongoing in vivo studies will test the utility of PLGA NP for treatment of these skin cancers.

Scientific Focus Area: ACI/IRS

This page was last updated on Monday, September 25, 2023