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金铂纳米颗粒制剂作为放疗的放射增敏剂具有双重作用。

Au-Pt Nanoparticle Formulation as a Radiosensitizer for Radiotherapy with Dual Effects.

机构信息

Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China.

Medical School of Nantong University, Nantong, Jiangsu, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Jan 12;16:239-248. doi: 10.2147/IJN.S287523. eCollection 2021.

Abstract

BACKGROUND

Radiotherapy occupies an essential position as one of the most significant approaches for the clinical treatment of cancer. However, we cannot overcome the shortcoming of X-rays which is the high value of the oxygen enhancement ratio (OER). Radiosensitizers with the ability to enhance the radiosensitivity of tumor cells provide an alternative to changing X-rays to protons and heavy ion radiotherapy.

MATERIALS AND METHODS

We prepared the Au-Pt nanoparticles (Au-Pt NPs) using a one-step method. The characteristics of the Au-Pt NPs were determined using TEM, HAADF-STEM, elemental mapping images, and DLS. The enhanced radiotherapy was demonstrated in vitro using MTT assays, colony formation assays, fluorescence imaging, and flow cytometric analyses of the apoptosis. The biodistribution of the Au-Pt NPs was analyzed using ICP-OES, and thermal images. The enhanced radiotherapy was demonstrated in vitro using immunofluorescence images, tumor volume and weigh, and hematoxylin & eosin (H&E) staining.

RESULTS

Polyethylene glycol (PEG) functionalized nanoparticles composed of the metallic elements Au and Pt were designed to increase synergistic radiosensitivity. The mechanism demonstrated that heavy metal NPs possess a high X-ray photon capture cross-section and Compton scattering effect which increased DNA damage. Furthermore, the Au-Pt NPs exhibited enzyme-mimicking activities by catalyzing the decomposition of endogenous HO to O in the solid tumor microenvironment (TME).

CONCLUSION

Our work provides a systematically administered radiosensitizer that can selectively reside in a tumor via the EPR effect and enhances the efficiency of treating cancer with radiotherapy.

摘要

背景

放射疗法作为癌症临床治疗的最重要方法之一,占有重要地位。然而,我们无法克服 X 射线的一个缺点,即氧增强比(OER)值较高。具有增强肿瘤细胞放射敏感性能力的放射增敏剂为改变 X 射线为质子和重离子放射疗法提供了一种替代方法。

材料和方法

我们使用一步法制备了金-铂纳米颗粒(Au-Pt NPs)。使用 TEM、HAADF-STEM、元素映射图像和 DLS 确定 Au-Pt NPs 的特性。通过 MTT 测定、集落形成测定、荧光成像和细胞凋亡的流式细胞术分析,在体外证明了增强放射治疗。使用 ICP-OES 和热图像分析 Au-Pt NPs 的生物分布。通过免疫荧光图像、肿瘤体积和重量以及苏木精和伊红(H&E)染色,在体外证明了增强放射治疗。

结果

设计了由金属元素 Au 和 Pt 组成的聚乙二醇(PEG)功能化纳米颗粒,以提高协同放射敏感性。该机制表明,重金属 NPs 具有高 X 射线光子俘获截面和康普顿散射效应,可增加 DNA 损伤。此外,Au-Pt NPs 通过在实体瘤微环境(TME)中催化内源性 HO 分解为 O,表现出酶模拟活性。

结论

我们的工作提供了一种系统管理的放射增敏剂,可通过 EPR 效应选择性地驻留在肿瘤中,并提高放射治疗治疗癌症的效率。

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