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Graphene-sandwiched DNA nano-system: Regulation of intercalated doxorubicin for controlled cellular localization

Abstract

Control of the sub-cellular localization of nanoparticles (NPs) with enhanced drug-loading capacity, employing graphene oxide (GO), iron oxide (Fe3O4) NPs and sandwiched deoxyribonucleic acid (DNA) bearing intercalated anticancer drug doxorubicin (DOX) have been implicated. The nanosystems G-DNA-DOX- Fe3O4 and Fe3O4-DNA-DOX differentially influence serum protein binding and deliver DOX to lysosomal compartments of cervical cancer (HeLa) cells with enhanced retention. Stern-Volmer plots describing bovine serum albumin (BSA) adsorption on the nanosystems demonstrated quenching constants, Ksv for G-DNA-DOX- Fe3O4 and Fe3O4-DNA-DOX (0.025 ml.μg-1 and 0.0103 ml.μg-1 respectively. Nuclear DOX intensity accounted at 24 h, was ~2.0 fold higher for Fe3O4-DNA-DOX in HeLa cells. Parallelly, the cytosol displayed ~2.2 fold higher DOX intensity for sandwiched Fe3O4-DNA-DOX sytem compared to G-DNA-DOX- Fe3O4 and showed higher cytotoxicity efficiency over to free Dox. The results implicate DNA:DOX NPs in influencing cellular uptake mechanism and were critically subject to cellular localization. Furthermore, cell morphology analysis evidenced the maximum cell deformation attributed to free-DOX with 34% increased cell roundness, 63% decreased cell area and ~1.9 times increased nuclear-to-cytoplasmic (N/C) ratio after 24 h. On the other hand, Fe3O4-DNA-DOX, the N/C ratio increased 1.2 times and ~37% decrease in NSA was accounted suggesting the involvement of non-canonical cytotoxic pathways. In conclusion, the study makes a case for designing nanosystems to achieve regulated, defined, and controlled sub-cellular localization for enhanced anticancer efficacy and reduced adverse effects.

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Supplementary files

Article information


Submitted
13 Jul 2020
Accepted
05 Oct 2020
First published
05 Oct 2020

This article is Open Access

Nanoscale Adv., 2020, Accepted Manuscript
Article type
Paper

Graphene-sandwiched DNA nano-system: Regulation of intercalated doxorubicin for controlled cellular localization

S. Nandi, N. R. Kale, A. Patil, S. S. Banerjee, Y. N. Patil and J. Khandare, Nanoscale Adv., 2020, Accepted Manuscript , DOI: 10.1039/D0NA00575D

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