DNA Damage and Apoptosis Induction in Cancer Cells by Chemically Engineered Thiolated Riboflavin Gold Nanoassembly.
Abhishek SauSulagna SanyalKallol BeraSabyasachi SenAmrit Krishna MitraSubham DasguptaPrabal Kumar ChakrabortySayantan GangulyBiswarup SatpatiChandrima DasSamita BasuPublished in: ACS applied materials & interfaces (2018)
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.
Keyphrases
- cell cycle arrest
- cell death
- dna damage
- molecular dynamics
- cancer therapy
- pi k akt
- gene expression
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- signaling pathway
- drug delivery
- dna methylation
- aqueous solution
- long non coding rna
- circulating tumor
- cell proliferation
- cell free
- poor prognosis
- single cell
- emergency department
- quantum dots
- cell therapy