Gándola Yamila B, Pérez Sebastián E, Irene Pablo E, Sotelo Ana I, Miquet Johanna G, Corradi Gerardo R, Carlucci Adriana M, Gonzalez Lorena
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Biomed Res Int. 2014;2014:687037. doi: 10.1155/2014/687037. Epub 2014 Mar 20.
Lecithins, mainly composed of the phospholipids phosphatidylcholines (PC), have many different uses in the pharmaceutical and clinical field. PC are involved in structural and biological functions as membrane trafficking processes and cellular signaling. Considering the increasing applications of lecithin-based nanosystems for the delivery of therapeutic agents, the aim of the present work was to determine the effects of phosphatidylcholine nanoparticles over breast cancer cellular proliferation and signaling. PC dispersions at 0.01 and 0.1% (w/v) prepared in buffer pH 7.0 and 5.0 were studied in the MCF-7 breast cancer cell line. Neutral 0.1% PC-derived nanoparticles induced the activation of the MEK-ERK1/2 pathway, increased cell viability and induced a 1.2 fold raise in proliferation. These biological effects correlated with the increase of epidermal growth factor receptor (EGFR) content and its altered cellular localization. Results suggest that nanoparticles derived from PC dispersion prepared in buffer pH 7.0 may induce physicochemical changes in the plasma membrane of cancer cells which may affect EGFR cellular localization and/or activity, increasing activation of the MEK-ERK1/2 pathway and inducing proliferation. Results from the present study suggest that possible biological effects of delivery systems based on lecithin nanoparticles should be taken into account in pharmaceutical formulation design.
卵磷脂主要由磷脂酰胆碱(PC)组成,在制药和临床领域有许多不同用途。PC参与结构和生物学功能,如膜运输过程和细胞信号传导。鉴于基于卵磷脂的纳米系统在治疗剂递送方面的应用日益增加,本研究的目的是确定磷脂酰胆碱纳米颗粒对乳腺癌细胞增殖和信号传导的影响。在MCF-7乳腺癌细胞系中研究了在pH 7.0和5.0的缓冲液中制备的0.01%和0.1%(w/v)的PC分散体。中性的0.1%源自PC的纳米颗粒诱导MEK-ERK1/2途径的激活,增加细胞活力并使增殖提高1.2倍。这些生物学效应与表皮生长因子受体(EGFR)含量的增加及其细胞定位的改变相关。结果表明,在pH 7.0的缓冲液中制备的PC分散体衍生的纳米颗粒可能会诱导癌细胞质膜的物理化学变化,这可能会影响EGFR的细胞定位和/或活性,增加MEK-ERK1/2途径的激活并诱导增殖。本研究结果表明,在药物制剂设计中应考虑基于卵磷脂纳米颗粒的递送系统可能产生的生物学效应。