Cellular uptake mechanism of an inorganic nanovehicle and its drug conjugates: Enhanced efficacy due to clathrin-mediated endocytosis |
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Authors: | Oh Jae-Min Choi Soo-Jin Kim Sang-Tae Choy Jin-Ho |
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Institution: | Center for Intelligent Nano-Bio Materials, Division of Nanoscience and Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea. |
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Abstract: | We present the mechanism for the cellular uptake of layered double hydroxide (LDH) nanoparticles that are internalized into MNNG/HOS cells principally via clathrin-mediated endocytosis. The intracellular LDHs are highly colocalized with not only typical endocytic proteins, such as clathrin heavy chain, dynamin, and eps15, but also transferrin, a marker of the clathrin-mediated process, suggesting their specific internalization pathway. LDHs loaded with an anticancer drug (MTX-LDH) were also prepared to confirm the efficacy of LDHs as drug delivery systems. The cellular uptake of MTX was higher in MTX-LDH-treated cells than in MTX-treated cells, giving a lower IC50 value for MTX-LDH than for MTX only. The inhibition of the cell cycle was greater for MTX-LDH than for MTX only. This result clearly shows that the internalization of LDH nanoparticles via clathrin-mediated endocytosis may allow the efficient delivery of MTX-LDH in cells and thus enhance drug efficacy. |
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