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载多柔比星的磁性金纳米粒子用于体内靶向药物递送。

Doxorubicin loaded magnetic gold nanoparticles for in vivo targeted drug delivery.

机构信息

Physics Department, Faculty of Science, King Abdulaziz University, Saudi Arabia; Biophysics Department, Faculty of Science, Cairo University, 12613 Giza, Egypt.

Biophysics Department, Faculty of Science, Cairo University, 12613 Giza, Egypt.

出版信息

Int J Pharm. 2015 Jul 25;490(1-2):190-9. doi: 10.1016/j.ijpharm.2015.05.032. Epub 2015 May 18.

Abstract

Treatment of approximately 50% of human cancers includes the use of chemotherapy. The major problem associated with chemotherapy is the inability to deliver pharmaceuticals to specific site of the body without inducing normal tissue toxicity. Latterly, magnetic targeted drug delivery (MTD) has been used to improve the therapeutic performance of the chemotherapeutic agents and reduce the severe side effects associated with the conventional chemotherapy for malignant tumors. In this study, we were focused on designing biocompatible magnetic nanoparticles that can be used as a nanocarrier's candidate for MTD regimen. Magnetic gold nanoparticles (MGNPs) were prepared and functionalized with thiol-terminated polyethylene glycol (PEG), then loaded with anti-cancer drug doxorubicin (DOX). The physical properties of the prepared NPs were characterized using different techniques. Transmission electron microscopy (TEM) revealed the spherical mono-dispersed nature of the prepared MGNPs with size about 22 nm. Energy dispersive X-ray spectroscopy (EDX) assured the existence of both iron and gold elements in the prepared nanoparticles. Fourier transform infrared (FTIR) spectroscopy assessment revealed that PEG and DOX molecules were successfully loaded on the MGNPs surfaces, and the amine group of DOX is the active attachment site to MGNPs. In vivo studies proved that magnetic targeted drug delivery can provide a higher accumulation of drug throughout tumor compared with that delivered by passive targeting. This clearly appeared in tumor growth inhibition assessment, biodistribution of DOX in different body organs in addition to the histopathological examinations of treated and untreated Ehrlich carcinoma. To assess the in vivo toxic effect of the prepared formulations, several biochemical parameters such as aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), urea, uric acid and creatinine were measured. MTD technology not only minimizes the random distribution of the chemotherapeutic agents, but also reduces their side effects to healthy tissues, which are the two primary concerns in conventional cancer therapies.

摘要

约 50%的人类癌症的治疗包括化疗的应用。化疗存在的主要问题是,无法将药物递送到身体的特定部位而不引起正常组织毒性。近来,磁性靶向药物递送(MTD)已被用于改善化疗药物的治疗效果,并降低与恶性肿瘤常规化疗相关的严重副作用。在这项研究中,我们专注于设计可作为 MTD 方案的纳米载体候选物的生物相容性磁性纳米颗粒。制备了磁性金纳米颗粒(MGNPs)并用巯基封端的聚乙二醇(PEG)进行功能化,然后负载抗癌药物阿霉素(DOX)。使用不同的技术对制备的 NPs 的物理性质进行了表征。透射电子显微镜(TEM)显示,制备的 MGNPs 具有约 22nm 的单分散球形。能量色散 X 射线光谱(EDX)确保了制备的纳米颗粒中存在铁和金元素。傅里叶变换红外(FTIR)光谱评估表明,PEG 和 DOX 分子已成功负载在 MGNPs 表面,并且 DOX 的氨基是与 MGNPs 发生活性连接的部位。体内研究表明,与被动靶向递送相比,磁性靶向药物递送可以在肿瘤中提供更高的药物积累。这在肿瘤生长抑制评估中,DOX 在不同身体器官中的分布以及未经处理和处理的 Ehrlich 癌的组织病理学检查中都有明显的表现。为了评估所制备配方的体内毒性作用,测量了几种生化参数,如天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、乳酸脱氢酶(LDH)、肌酸激酶 MB(CK-MB)、尿素、尿酸和肌酐。MTD 技术不仅最大限度地减少了化疗药物的随机分布,而且减少了它们对健康组织的副作用,这是常规癌症治疗中的两个主要关注点。

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