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

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
• multidrug resistance
• endocytosis
• intracellular transportation
• exocytosis

Acknowledgments

The authors are grateful to the Natural Science Foundation Committee of China for financial support (number 81202483 and number 81102400).

Disclosure

The authors report no conflicts of interest in this work.