Trafficking microenvironmental pHs of polycationic gene vectors in drug-sensitive and multidrug-resistant MCF7 breast cancer cells

作者：Kang Han Chang; Samsonova Olga; Bae You Han^*

来源：Biomaterials, 2010, 31(11): 3071-3078.

DOI：10.1016/j.biomaterials.2010.01.001

• Multidrug resistance
• pH trafficking
• Polyethyleneimine
• Poly(L-lysine)
• Polymeric gene delivery
• Solid tumors

While multidrug resistance (MDR) has been a significant issue in cancer chemotherapy, delivery resistance to various anti-cancer biotherapeutics, including genes, has not been widely recognized as a property of MDR. This study aims to provide a better understanding of the transfection characteristics of drug-sensitive and drug-resistant cells by tracing microenvironmental pHs of two representative polymer vectors: poly(L-lysine) and polyethyleneimine. Drug-sensitive breast MCF7 cells had four- to seven-times higher polymeric transfection efficiencies than their counterpart drug-resistant MCF7/ADR-RES cells. Polyplexes in MCF7/ADR-RES cells after endocytosis were exposed to a more acidic microenvironment than those in MCF7 cells; the MDR cells show faster acidification rates in endosomes/lysosomes than the drug-sensitive cells after endocytosis (in the case of PLL/pDNA complexes, similar to pH 5.1 for MCF7/ADR-RES cells vs. similar to pH 6.8 for MCF7 cells at 0.5 h post-transfection). More polyplexes were identified trapped in acidic subcellular compartments of MCF7/ADR-RES cells than in MCF7 cells, suggesting that they lack endosomal escaping activity. These findings demonstrate that the design of polymer-based gene delivery therapeutics should take into account the pH of subcellular compartments.

• 出版日期2010-4