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AS1411 适体-阴离子线性球形树枝状大分子 G2-碘海醇选择性纳米诊疗剂。

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics.

机构信息

Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Pilot Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Sci Rep. 2017 Sep 19;7(1):11832. doi: 10.1038/s41598-017-12150-8.

Abstract

Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.

摘要

分子治疗学在不同恶性肿瘤的诊断和治疗方面具有重要意义。本研究中,采用阴离子线性球形树枝状大分子 G2 作为载体,将 AS1411 适体作为靶向剂,将碘海醇特异性递送至人乳腺癌细胞(MCF-7)。制备了树枝状大分子 G2,并对其进行了偶联。基于原子力显微镜(AFM)的数据,当树枝状大分子与适体偶联时,原本光滑、球形的非靶向树枝状大分子的形态发生变化,变得粗糙、非球形。然后,使用 DLS、ELS 和 SLS 方法对其进行了确认。通过 XTT 和凋亡/坏死测定法评估了对核仁素阳性 MCF-7 细胞和核仁素阴性 HEK-293 细胞的毒性。通过 DAPI-FITC 染色和 ICP-MS 方法测定了细胞内摄取。进行了体内 CT 成像、病理学和血液检查等体内研究,以确认纳米治疗剂在体内的成像能力、生物安全性和靶向性。总之,所制备的结构在降低碘海醇对正常细胞的毒性、增加其在肿瘤中的积累以及减少癌细胞数量方面显示出了有希望的效果。

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