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Cell deformation and acquired drug resistance: elucidating the major influence of drug-nanocarrier delivery systems

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Abstract

Cancer diagnosis and its stage-wise assessment are determined through invasive solid tissue biopsies. Conversely, cancer imaging is enriched through emission tomography and longitudinal high-resolution analysis for the early detection of cancer through altered cell morphology and cell-deformation. Similarly, in post multiple chemo-cycle exposures, the tumor regression and progression thereafter are not well understood. Here, we report chemo-cycles of doxorubicin (Dox) carrying nanoparticles (NPs) to be highly indicative of cell deformation and a progressive indicator of phenotypic expressions of acquired drug resistance (ADR). We designed graphene (G) based nanocarriers by chemically conjugating multiple components: (i) G; (ii) iron oxide (Fe3O4) NPs; and (iii) Dox through a cysteine (Cys) linker (G-Dox and G-Cys-Fe3O4-Dox). Although Dox underwent cell diffusion, the G-based nanocarriers followed a receptor-mediated endocytosis which created a profound impact on the cell membrane integrity. ADR owing to Dox and G-based nanocarriers was analyzed through a cytotoxicity assay, cell morphology deformation parameters and cellular uptake kinetic patterns. Interestingly, after the third chemo-cycle, G-Dox incubated cells showed the greatest decrease in the alteration of the nuclear surface area (NSA) of ∼28%, a ∼40% reduction of the cell surface area (CSA) and a ∼32% increase in the cell roundness (CRd). Our results suggested that the G-based nanocarriers induced the cell deformation process, subsequently resulting in ADR. Although the G-based nanocarriers initiated ADR, G-Dox was most cytotoxic to cancer cells and induced the maximum cell morphology deformation within our scope of study. This outcome implies caution is needed when using G-based nanocarriers and other multi-component nanosystems for Dox delivery as they lead to possible phenotypic expressions of drug resistance in cancer cells.

Graphical abstract: Cell deformation and acquired drug resistance: elucidating the major influence of drug-nanocarrier delivery systems

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Supplementary files

Article information


Submitted
03 Dec 2019
Accepted
20 Jan 2020
First published
22 Jan 2020

J. Mater. Chem. B, 2020, Advance Article
Article type
Paper

Cell deformation and acquired drug resistance: elucidating the major influence of drug-nanocarrier delivery systems

S. Nandi, N. R. Kale, V. Takale, G. C. Chate, M. Bhave, S. S. Banerjee and J. J. Khandare, J. Mater. Chem. B, 2020, Advance Article , DOI: 10.1039/C9TB02744K

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