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