聚L-谷氨酸-γ-苄酯纳米粒子提高耐药细胞药物累积的研究

Poly(L-γ-glutamylglutamine) nanoparticles enhance drug accumulation in resistant cells

研究PGG载体在耐药肿瘤细胞中的作用.通过诱导A549细胞产生多药耐药性,评估在耐药肿瘤细胞中PGG对抗癌药物多柔比星胞内累积和驻留的影响.证明PGG药物输送系统能够增加耐药细胞株中的药物累积.利用内吞抑制试验和透射电镜试验阐明细胞通过胞饮方式摄取PGG载体药物,该方式提高了药物的细胞摄取,增加了药物的细胞累积.并利用激光共聚焦显微术确认了药物的细胞累积.PGG-Dox同游离Dox相比,通过胞饮作用进入细胞后,可以显著增加药物处理细胞内的Dox累积和驻留.Dox与PGG药物输送系统连接后,具有显著的抗耐药效果.PGG药物输送系统具备应用于耐药型肿瘤治疗的潜力.

This work investigated the antitumor efficacy of poly （L-γ-glutamylglutamine） （PGG） prodrug in multidrug resistant （MDR） cancer cells and the possible mechanisms.The A549 cell line was induced to become multidrug resistant.A549 was applied to evaluate the effect of PGG-Dox on intracellular accumulation and retention of Dox.Endocytosis inhibition studies and transmission electron microscope assay were used to investigate the mechanisms of cellular PGG-Dox uptake.Confocal laser scanning microscopy was performed to confirm the drug accumulation.Treatment of MDR cells with PGG-Dox resulted in significantly enhanced drug accumulation and retention after the end of treatment compared with free Dox.Endocytosis inhibition studies showed pinocytosis is the mainly pathway in the elevated membrane permeability of the PGG-Dox.These demonstrated that Dox conjugate with PGG NPs effectively bypass the multidrug resistance.Our PGG DDS may be considered as an attractive and promising delivery system to overcome multidrug resistance.