Nanoparticle encapsulation of HDACi with HA targeting in endometrial cancer models

Abstract

Bespoke nanoparticle systems can enhance drug delivery, preventing systemic exposure by modifying release kinetics and increasing tumour penetration. Flexible nano vector systems have led to selective tumour targeting through surface modifications and the addition of target moieties over expressed in the cancer microenvironment. As such nanomedicines are enabling drug re-purposing and renewed applications in solid tumour cancers. Here we present the nanoscale encapsulation of Vorinostat within a F127 Pluronic polymer particle modified to incorporate a Hyaluronic Acid moiety, targeting increased CD44 expression in endometrial cancer cells. Encapsulation within a stable micellar structure stabilized SAHA activity, demonstrating increased cytotoxic efficacy in 2-D and 3-D cultures. In addition, nano delivery enhanced spheroid penetration, suppression in cell growth, P21 associated cell cycle arrest and overcome EMT associated phenotype formation observed in the free drug treated type II Hec50 cells. Together, this study clearly demonstrates that HDAC nanoparticle encapsulation and HA targeting may offer a solution to overcoming the toxicity and side effects issues observed in clinical trials. Given the demonstrated involvement of epigenetic processes in oncology, this study is an important demonstration of this class of anti-cancerous agents for the treatment of endometrial cancers.