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

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. S...

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Veröffentlicht in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2020-03, Vol.8 (9), p.1852-1862
Hauptverfasser: Nandi, Semonti, Kale, Narendra R, Takale, Vijay, Chate, Govind C, Bhave, Madhura, Banerjee, Shashwat S, Khandare, Jayant J
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Sprache:eng
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Zusammenfassung: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 (Fe 3 O 4 ) NPs; and (iii) Dox through a cysteine (Cys) linker (G-Dox and G-Cys-Fe 3 O 4 -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. Chemo-cycles of doxorubicin-nanocarriers are reported to be highly indicative of cell deformations and are a progressive indicator of acquired drug resistance.
ISSN:2050-750X
2050-7518
DOI:10.1039/c9tb02744k