Herein we have engineered
a smart nuclear targeting thiol-modified riboflavin-gold nano assembly, RfS@AuNPs, which accumulates selectively in the nucleus without
any nuclear-targeting peptides (NLS/RGD) and shows photophysically
in vitro DNA intercalation. A theoretical model using Molecular Dynamics
has been developed to probe the mechanism of formation and stability
as well as dynamics of the RfS@AuNPs in aqueous solution
and within the DNA microenvironment. The RfS@AuNPs facilitate
the binucleated cell formation that is reflected in the significant
increase of DNA damage marker, γ-H2AX as well as the arrest
of most of the HeLa cells at the pre-G1 phase indicating cell death.
Moreover, a significant upregulation of apoptotic markers confirms
that the cell death occurs through the apoptotic pathway. Analyses
of the microarray gene expression of RfS@AuNPs treated
HeLa cells show significant alterations in vital biological processes
necessary for cell survival. Taken together, our study reports a unique
nuclear targeting mechanism through targeting the riboflavin receptors,
which are upregulated in cancer cells and induce apoptosis in the
targeted cells.