Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor.
Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor.
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瞄准细胞内靶标，用于递送用组蛋白脱乙酰酶抑制剂功能化的负载纳米颗粒
DOI：
10.18632/oncotarget.20021
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Lu W
中科院分区：
文献类型：
--
作者：
Zhang J;Shi Y;Zheng Y;Pan C;Yang X;Dou T;Wang B;Lu W
功能化纳米粒(NPs)通常被用来增强细胞的渗透性，从而靶向递送药物，从而提高疗效并减少副作用。然而，很难利用细胞内的靶点来实现类似的递送应用。在这里，我们描述了通过定位于细胞内的靶点组蛋白脱乙酰酶(HDAC)来靶向传递功能化的NPs。具体地说，通过与HDAC抑制剂偶联得到了一种改性的聚丙交酯-乙交酯共聚物(FPLGA)。随后，将FPLGA用于制备功能化的FPLGA纳米粒子。与未修饰的纳米粒相比，FPLGA纳米粒能更有效地被MCF-7细胞摄取或保留，并显示出更长的细胞内保留时间。体内荧光成像还显示，与未修饰的纳米粒相比，它们具有更高的蓄积量和更慢的消除速度。与未修饰的纳米粒相比，载紫杉醇的FPLGA纳米粒具有更好的抗癌效果。这些结果为通过提高纳米粒浓度实现细胞内给药提供了一种很有前途的途径。
Functionalized nanoparticles (NPs) are usually used to enhance cellular penetration for targeted drug delivery that can improve efficacy and reduce side effects. However, it is difficult to exploit intracellular targets for similar delivery applications. Herein we describe the targeted delivery of functionalized NPs by homing in on an intracellular target, histone deacetylases (HDACs). Specifically, a modified poly-lactide-co-glycolideacid (FPLGA) was yielded by conjugation with an HDAC inhibitor. Subsequently, FPLGA was used to prepare functionalized FPLGA NPs. Compared to unmodified NPs, FPLGA NPs were more efficiently uptaken or retained by MCF-7 cells and showed longer retention time intracellular. In vivo fluorescence imaging also revealed that they had a higher accumulation and a slower elimination than unmodified NPs. FPLGA NPs loaded with paclitaxel exhibited superior anticancer efficacy compared with unmodified NPs. These results offer a promising approach for intracellular drug delivery through elevating the concentration of NPs.
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