Core-shell nanofibre scaffold mediated co-delivery of connexin-43 gene and histone deacetylase inhibitor for anticancer therapy

Abstract

Connexin 43 (Cx43), a gap junction protein, also acts as a tumor suppressor, which reduces tumorigenicity. Cx43 expression sensitizes cancer cells towards anticancer drugs mainly due to the formation of functional gap junctions. 4-phenyl butyrate (4-PB), a histone deacetylase inhibitor (HDACi), has antitumor potential that is also reported to increase Cx43 expression and gap junction communication. In the present work, we have developed a core-shell nanofibrous scaffold loaded with the Cx43 gene and 4-PB. The nanofibrous scaffold has been characterized by spectroscopic and electron microscopic techniques. The nanofibrous scaffold mediated transfection of the Cx43 gene into Cx43 deficient breast cancer cells (MCF-7), followed by controlled and sustained release of 4-PB, exhibited anti-cell proliferative activity. The anticancer effects have been ascertained by cell staining, cell viability and flow cytometry-based assays. Thus, the novel core-shell nanofiber scaffold has shown enormous therapeutic translation ability via Cx-based enhancement of anticancer potential of HDACi.