Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Carbohydr Polym. 2018 Oct 1;197:157-166. doi: 10.1016/j.carbpol.2018.05.092. Epub 2018 Jun 1.
To efficiently deliver the chemotherapeutics to the tumor tissue and minimize the associated adverse effects, nucleolin targeted hybrid nanostructure based on hollow mesoporous silica nanoparticles (HMSNs) were fabricated. To provide the controlled, sustained drug release and enhance blood circulation, the surface of doxorubicin-encapsulated HMSNs were coated with acetylated carboxymethyl cellulose (Ac-CMC) and then covalently conjugated to AS1411 aptamer for guided drug delivery to nucleolin overexpressed cancerous cells. In vitro cellular uptake and cytotoxicity studies confirmed that AS1411 aptamer specifically targets nucleolin overexpressing MCF-7 and C26 cells. Moreover, the in vivo tumor inhibitory effect of AS1411 aptamer conjugated formulation demonstrated a superior therapeutic efficiency over non-targeted formulation and free doxorubicin. The current study might open a new insight to the development of targeted intelligent hybrid materials based on AcCMC-coated HMSNs with high loading capacity, smart characteristics and desirable anticancer potential.
为了高效地将化疗药物递送到肿瘤组织并最小化相关的不良反应，我们制备了基于中空介孔硅纳米粒子（HMSNs）的核仁素靶向杂化纳米结构。为了提供控制的、持续的药物释放并增强血液循环，阿霉素包封的 HMSNs 的表面用乙酰化羧甲基纤维素（Ac-CMC）进行涂层，然后与 AS1411 适体共价偶联，以引导药物递送到核仁素过表达的癌细胞。体外细胞摄取和细胞毒性研究证实，AS1411 适体特异性靶向核仁素过表达的 MCF-7 和 C26 细胞。此外，AS1411 适体偶联制剂的体内肿瘤抑制效果显示出比非靶向制剂和游离阿霉素更高的治疗效率。本研究可能为基于 AcCMC 涂层 HMSNs 的靶向智能杂化材料的开发提供新的思路，这些材料具有高载药能力、智能特性和理想的抗癌潜力。
