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Issue 9, 2020
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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, 2020,8, 1852-1862
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, 8, 1852
DOI: 10.1039/C9TB02744K

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