Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University Kawagoe, Saitama, Japan.
Biotechnol Bioeng. 2012 Nov;109(11):2920-31. doi: 10.1002/bit.24558. Epub 2012 Jun 1.
Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery.
脂质体和聚合物作为控释药物载体得到了广泛应用，因为它们具有许多优点，如提高治疗效果、降低毒性，并且具有生物可降解性。在这项工作中，合成了载有抗癌药物的 PLGA-卵磷脂-PEG 纳米粒子（NPs），并用 AS1411 抗核仁素适体对其进行功能化，以实现对过度表达核仁素受体的肿瘤细胞的特异性靶向。通过透射电子显微镜（TEM）和 X 射线光电子能谱（XPS）对颗粒进行了表征。采用紫外光谱法进行了载药效率、包封效率和体外药物释放研究。在两种不同的癌细胞系 MCF-7 和 GI-1 细胞以及两种不同的正常细胞 L929 细胞和 HMEC 细胞中进行了细胞毒性研究。共聚焦显微镜和流式细胞术证实了颗粒的细胞摄取和靶向药物递送。NPs 的形态分析证明，颗粒呈光滑球形，粒径在 60 至 110nm 之间。载药研究表明，在相同的载药量下，与相应的非靶向 NPs 相比，适配体靶向 NPs 显示出增强的抗癌杀伤效果。此外，PLGA-卵磷脂-PEG NPs 表现出高包封效率和优于载药的 PLGA NPs 的持续药物释放。结果证实，AS1411 适配体-PLGA-卵磷脂-PEG NPs 是差异化靶向药物递送的潜在载体候选物。
