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一种实现小尺寸改性金纳米颗粒高效细胞摄取与保留以用于细胞放射增敏的方法。

A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells.

作者信息

Burger Nina, Biswas Abin, Barzan Daniel, Kirchner Anne, Hosser Hiltraud, Hausmann Michael, Hildenbrand Georg, Herskind Carsten, Wenz Frederik, Veldwijk Marlon R

机构信息

Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Kirchhoff-Institut for Physics, University of Heidelberg, Heidelberg, Germany.

出版信息

Nanomedicine. 2014 Aug;10(6):1365-73. doi: 10.1016/j.nano.2014.03.011. Epub 2014 Mar 25.

Abstract

UNLABELLED

Gold nanoparticles (GNP) enhance the absorbance of photons thereby increasing emission of Auger-/photoelectrons in the nm-μm range. Yet, a major disadvantage is their diameter-dependent cellular uptake with an optimum of ~50 nm which may not offer optimal radiosensitization. A method was developed to enhance the uptake of small GNP. GNP (10nm) were linked to DNA and transferred into HeLa cells by transient transfection (GNP-DT). Treatment of cells with GNP-DT resulted in a strong perinuclear focal accumulation, whereas this was dimmer and sparser for GNP-T (lacking DNA) and close to background levels in GNP-treated cells. Only GNP-DT showed a significant radiosensitizing effect (p=0.005) on clonogenic survival using clinically relevant megavolt x-rays. Our novel method markedly increases the uptake/retention and alters the localization of small GNP in cells compared to unmodified GNP. This work finally enables studying the radiosensitizing effects of differentially sized GNP.

FROM THE CLINICAL EDITOR

In an effort to increase the radiosensitization of HeLa cells, his paper discusses a transient transfection-based method to enhance gold nanoparticle intracellular delivery.

摘要

未标记

金纳米颗粒(GNP)可增强光子吸收,从而增加纳米至微米范围内俄歇电子/光电子的发射。然而,一个主要缺点是它们的细胞摄取依赖于直径,最佳直径约为50nm,这可能无法提供最佳的放射增敏效果。已开发出一种方法来增强小尺寸GNP的摄取。将GNP(10nm)与DNA连接,并通过瞬时转染(GNP-DT)转入HeLa细胞。用GNP-DT处理细胞导致强烈的核周灶性聚集,而对于GNP-T(不含DNA)则较暗淡且稀疏,在GNP处理的细胞中接近背景水平。使用临床相关的兆伏级X射线,仅GNP-DT对克隆形成存活显示出显著的放射增敏作用(p = 0.005)。与未修饰的GNP相比,我们的新方法显著增加了小尺寸GNP在细胞中的摄取/保留,并改变了其在细胞内的定位。这项工作最终使得研究不同尺寸GNP的放射增敏作用成为可能。

临床编辑评论

为了提高HeLa细胞的放射增敏作用,本文讨论了一种基于瞬时转染的方法来增强金纳米颗粒的细胞内递送。

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