Mechanism of cellular uptake and cytotoxicity of paclitaxel loaded lipid nanocapsules in breast cancer cells

Valsalakumari, Remya and Yadava, Sunil Kumar and Szwed, Marzena and Pandya, Abhilash D. and Mælandsmo, Gunhild Mari and Torgersen, Maria Lyngaas and Iversen, Tore-Geir and Skotland, Tore and Sandvig, Kirsten and Giri, Jyotsnendu (2021) Mechanism of cellular uptake and cytotoxicity of paclitaxel loaded lipid nanocapsules in breast cancer cells. International Journal of Pharmaceutics, 597 (120217). p. 120217. ISSN 03785173

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Abstract

Lipid nanocapsules (LNCs) have proven their efficacy in delivering different drugs to various cancers, but no studies have yet described their uptake mechanisms, paclitaxel (PTX) delivery or resulting cytotoxicity towards breast cancer cells. Herein, we report results concerning cellular uptake of LNCs and cytotoxicity studies of PTX-loaded LNCs (LNCs-PTX) on the three breast cancer cell lines MCF-7, MDA-MB-231 and MDA-MB-468. LNCs-PTX of sizes 50 ± 2 nm, 90 ± 3 nm and 120 ± 4 nm were developed by the phase inversion method. Fluorescence microscopy and flow cytometry were used to observe the uptake of fluorescently labeled LNCs and cellular uptake of LNCs-PTX was measured using HPLC analyses of cell samples. These studies revealed a higher uptake of LNCs-PTX in MDA-MB-468 cells than in the other two cell lines. Moreover, free PTX and LNCs-PTX exhibited a similar pattern of toxicity towards each cell line, but MDA-MB-468 cells appeared to be more sensitive than the other two cell lines, as evaluated by the MTT cytotoxicity assay and a cell proliferation assay based upon [3H]thymidine incorporation. Studies with inhibitors of endocytosis indicate that the cellular uptake is mainly via the Cdc42/GRAF-dependent endocytosis as well as by macropinocytosis, whereas dynamin-dependent processes are not required. Furthermore, our results indicate that endocytosis of LNCs-PTX is important for the toxic effect on cells. Western blot analysis revealed that LNCs-PTX induce cytotoxicity by means of apoptosis in all the three cell lines. Altogether, the results demonstrate that LNCs-PTX exploit different mechanisms of endocytosis in a cell-type dependent manner, and subsequently induce apoptotic cell death in the breast cancer cells here studied. The article also describes biodistribution studies following intravenous injection of fluorescently labeled LNCs in mice.

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IITH Creators:

IITH Creators	ORCiD
Valsalakumari, Remya	UNSPECIFIED
Yadava, Sunil Kumar	UNSPECIFIED
Giri, Jyotsnendu	UNSPECIFIED

Item Type:

Article

Uncontrolled Keywords:

animal cell; animal experiment; animal model; apoptosis; Article; breast cancer; breast cancer cell line; cell proliferation assay; controlled study; cytotoxicity assay; dispersity; DNA synthesis; drug uptake; endocytosis; female; flow cytometry; fluorescence microscopy; high performance liquid chromatography; human; human cell; lipid transport; macropinocytosis; MCF-7 cell line; MDA-MB-231 cell line; MDA-MB-468 cell line; mouse; nanoencapsulation; nonhuman; particle size; priority journal; Western blotting; animal; breast tumor; tissue distribution; tumor cell line

Subjects:

Biomedical Engineering

Divisions:

Department of Biomedical Engineering

Depositing User:

. LibTrainee 2021

Date Deposited:

02 Aug 2021 04:22

Last Modified:

02 Aug 2021 04:22

URI:

http://raiithold.iith.ac.in/id/eprint/8622