Abstract
Connexin (Cx), a gap junction protein plays an important role in cancer pathophysiology. The enhancement of Cx43, an isoform of Cx, has been reported to improve survival of patients with breast cancer. Since Cxs are expressed in various tissues and organs, their localized modulation is necessary to achieve therapeutic benefits without any side-effects. Therapy combined with diagnostics, i.e. theranostics, is becoming an important facet of cancer management. Thus, considering these two critical aspects, the present study deals with synthesis, bio-imaging, and anti-proliferative effects of a multi-functional chitosan hydrogel incorporating highly fluorescent silver nanoclusters and 4-phenylbutyrate, a histone deacetylase inhibitor for enhancing Cx43 expression. While the remarkable fluorescence of silver nanoclusters enabled cellular uptake and imaging, 4-phenylbutyrate released from the hydrogel specifically upregulated Cx43 expression and induced apoptosis in breast cancer cells. Moreover, the 4-phenylbutyrate released, successfully established gap junction communication between cancer cells as assessed by dye transfer assay. Thus, the current module not only holds potential in cancer theranostics but also for Cx-based cancer therapeutics.
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