DNA Damage and Apoptosis Induction in Cancer Cells by Chemically Engineered Thiolated Riboflavin Gold Nanoassembly

• Published in: ACS applied materials & interfaces 2018-02, Vol.10 (5), p.4582-4589
• Main Authors: Sau, Abhishek, Sanyal, Sulagna, Bera, Kallol, Sen, Sabyasachi, Mitra, Amrit Krishna, Pal, Uttam, Chakraborty, Prabal Kumar, Ganguly, Sayantan, Satpati, Biswarup, Das, Chandrima, Basu, Samita
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Line, Tumor; DNA Damage; Gold; HeLa Cells; Humans; Riboflavin
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.7b18837

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.