Abstract
The tuning of physicochemical properties like particle sizes, surface modifications, etc., is essential to improve delivery efficiency with insignificant toxicity. A quantitative and mechanistic investigation on cellular uptake and intracellular trafficking of fluorescent-labeled polystyrene particles [50 and 500 nm plain and 200 nm and 1 µm carboxylate-coated polystyrene (PPS and CPS)] against breast cancer cells was performed. Examinations of cell proliferation, viability, and cytotoxicity indicated that those applied polymeric particles at concentrations of 4–40 µg/mL are non-toxic to cells except 200 nm CPS (16 µg/mL) which partially reduced cell viability. Quantitative fluorescent microscopy revealed that 200 nm CPS displayed the highest capability to be internalized by MCF-7 cells, in which the average intracellular particles are about 14 and 35 folds higher than 1 µm CPS and 500 nm PPS, respectively. Analysis of the uptake routes using inhibitors provided clear evidence that 200 CPS was mainly ingested via the clathrin-mediated endocytosis, whereas larger particles (> 500 nm) preferentially utilized the macropinocytosis pathway. Fluorescent live-cell imaging suggested that particles were mainly internalized by cells in an individual form instead of large aggregates, despite late occurrence of partial agglomeration in the cytoplasm. Overall, those outcomes enhanced our understanding of the application of polymeric delivery vehicles for the treatment of breast cancer.
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Acknowledgements
This work was supported to Dr. Jie Chen by the National Natural Science Foundation of China (81600063) and Natural Science Foundation of Hunan Province (2017JJ3484).
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Video 1, 2, and 3: Cellular uptake and dynamic and intracellular redistribution of 500 nm plain polystyrene particles and 200 nm and 1 μm carboxylate-coated polystyrene particles incubated individually with MCF-7 cells obtained by fluorescence and bright field live-cell imaging. (AVI 1734 kb)
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Zhou, Mr., Xie, Pf., Gong, J. et al. Mechanistic investigation of cellular internalization routes of polymeric particles on breast cancer cells: relevance for drug delivery applications. Appl Nanosci 10, 2239–2254 (2020). https://doi.org/10.1007/s13204-020-01376-0
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DOI: https://doi.org/10.1007/s13204-020-01376-0