ABSTRACT

In this study, we grafted hydrophilic γ-polyglutamic acid (γ-PGA) with the hydrophobic drug methotrexate (MTX) to develop an amphiphilic and stimuli-responsive nanoparticles (MTX-SS-PGA NPs). The average size and zeta potential for MTX-SS-PGA NPs were 100.5 nm and −20.4 mV. In vitro drug release, the MTX cumulative release of nanoparticles within 72 h, which was more robust at 10 mM GSH (90.1%) than normal physiological environment pH 7.4 (9.8%). The disulphide bond was easily cleaved by glutathione, which subsequently led to the disintegration of the nanoparticle structure and the release of MTX. In cell studies, 10 μM MTX-SS-PGA NPs was efficient taken up into the cancer cell, released MTX in a redox-responsive manner, and exhibited cytotoxicity as potent as MTX.Moreover, 10 μM MTX-SS-PGA NPs have little side effects on normal cells. Overall, this new type of glutathione-responsive anti-osteosarcoma prodrug nanoparticles is promising for efficient drug delivery.

摘要

在这项研究中，我们将亲水性 γ-聚谷氨酸 (γ-PGA) 与疏水性药物甲氨蝶呤 (MTX) 接枝，以开发两亲性和刺激响应纳米粒子 (MTX-SS-PGA NPs)。MTX-SS-PGA NPs 的平均尺寸和 zeta 电位为 100.5 nm 和 -20.4 mV。体外药物释放，纳米颗粒在 72 小时内 MTX 累积释放，在 10 mM GSH (90.1%) 下比正常生理环境 pH 7.4 (9.8%) 更稳健。二硫键很容易被谷胱甘肽裂解，随后导致纳米颗粒结构的解体和MTX的释放。在细胞研究中，10 μM MTX-SS-PGA NPs 可有效吸收到癌细胞中，以氧化还原响应方式释放 MTX，并表现出与 MTX 一样强的细胞毒性。此外，10 μM MTX-SS-PGA NPs 几乎没有对正常细胞的副作用。全面的，