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智能炸弹AS1411适配体功能化/聚酰胺-胺树枝状大分子纳米载体用于胃癌治疗中的靶向药物递送。

Smart bomb AS1411 aptamer-functionalized/PAMAM dendrimer nanocarriers for targeted drug delivery in the treatment of gastric cancer.

作者信息

Barzegar Behrooz Amir, Nabavizadeh Fatemeh, Adiban Jamal, Shafiee Ardestani Mehdi, Vahabpour Rouhollah, Aghasadeghi Mohammad Reza, Sohanaki Hamid

机构信息

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Biomedical Engineering and Medical physics, Department of Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Clin Exp Pharmacol Physiol. 2017 Jan;44(1):41-51. doi: 10.1111/1440-1681.12670.

DOI:10.1111/1440-1681.12670
PMID:27626786
Abstract

Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer-based pharmaceutical system together with a single-stranded AS1411 aptamer (APT ) as a therapeutic strategy. The polyamidoamine (PAMAM)-polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic-force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM-PEG-APT complex dramatically increased PAMAM-PEG-5-FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle-5-FU-APT complex, by thin layer chromatography (TLC), and an increase in 5-fluorouracil (5-FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5-FU to MKN45 gastric cancer cells in consistent and without toxic effects.

摘要

化疗是近期肿瘤学研究中评估的一种传统方法,在临床环境中存在诸多问题。为克服化疗固有的问题,智能药物递送系统已成为癌症治疗的前沿领域。在本研究中,我们设计了一种基于树枝状聚合物的药物系统,并将单链AS1411适配体(APT)作为一种治疗策略。然后将聚酰胺胺(PAMAM)-聚乙二醇(PEG)复合物与AS1411适配体偶联,并通过原子力显微镜(AFM)和傅里叶变换红外光谱(FTIR)进行确认。在本研究中,我们表明偶联的PAMAM-PEG-APT复合物显著增加了MKN45胃癌细胞对PAMAM-PEG-5-氟尿嘧啶的摄取。我们还通过薄层色谱(TLC)证明了纳米颗粒-5-氟尿嘧啶-APT复合物的稳定性,以及癌性肿瘤附近5-氟尿嘧啶(5-FU)积累的增加。这种智能药物递送系统能够有效地将5-FU持续且无毒性地转移至MKN45胃癌细胞。

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