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Int J Nanomedicine. 2016 Aug 3;11:3677-90. doi: 10.2147/IJN.S106418. eCollection 2016.

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells.

Author information

1
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
2
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; Department of Pharmaceutics, School of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People's Republic of China.

Abstract

Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells.

KEYWORDS:

PAMAM dendrimers; endocytosis; exocytosis; intracellular transportation; multidrug resistance

PMID:
27536106
PMCID:
PMC4977074
DOI:
10.2147/IJN.S106418
[Indexed for MEDLINE]
Free PMC Article

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