DNA Damage and Apoptosis Induction in Cancer Cells by Chemically Engineered Thiolated Riboflavin Gold Nanoassembly
Abstract
Herein we have engineered a smart nuclear targeting thiol-modified riboflavin-gold nano assembly, RfS@AuNPs, which accumulates selectively in 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 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 pre-G1 phase indicating cell death. Moreover, a significant upregulation of apoptotic markers confirms that the cell death occurs through 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.
Additional Information
© 2018 American Chemical Society. Received: December 11, 2017; Accepted: January 16, 2018; Published: January 16, 2018. We sincerely thank S. Haldar, R. Modok, Y. Sikdar, C. Sengupta, P. Mitra, S. Das Chakraborty, and M. Bhattacharyya for their constant support and help. We acknowledge financial support from UGC (A.S.); F2-32/1998 (SA-1), DBT- Government of India, Ramalingaswami fellowship and BARD project: DAE at Saha Institute of Nuclear Physics. The authors declare no competing financial interest.Attached Files
Supplemental Material - am7b18837_si_001.pdf
Supplemental Material - am7b18837_si_002.avi
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Supplemental Material - am7b18837_si_005.avi
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Additional details
- Eprint ID
- 84358
- Resolver ID
- CaltechAUTHORS:20180117-092127661
- F2-32/1998
- University Grants Commission (India)
- Department of Biotechnology (India)
- Department of Atomic Energy (India)
- Created
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2018-01-17Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field