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富勒醇组装阿霉素增强载药纳米载体的化疗增效减毒作用及其机制

Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and side effects reduction in chemotherapy by using fullerenol assembled with doxorubicin.

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China; School of Public Health, Qingdao University, Qingdao 226021, China.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China; Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

出版信息

Biomaterials. 2018 Jun;167:205-215. doi: 10.1016/j.biomaterials.2018.03.015. Epub 2018 Mar 12.

Abstract

Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects. We utilized fullerenol as a "histone", packaged a great number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome" (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the encapsulation efficiency of Dox in the polymeric micelles was increased from ∼5% to ∼79%. What's more, the biomimetic-inspired delivery system significantly reduced the chemodrug side effects by utilizing the radical scavenging ability of fullerenol. This novel drug-delivery design approach provides useful insights for improving the applicability of fullerenol in drug delivery systems for cancer therapy.

摘要

化学药物被广泛用于治疗癌症;然而,化疗通常会导致严重的副作用和失败。为了提高化学药物的疗效,已经探索了各种纳米材料和策略来进行药物输送。将化学药物装载到纳米递药系统中的关键之一是提高包封效率,特别是对于负载亲水性药物的聚合物纳米粒。受真核生物在细胞核中包装数百万个基因的能力的启发,我们将核蛋白体样杂化纳米颗粒用于包裹和浓缩 DNA 形成染色体,以实现阿霉素(DOX)的超高包封,同时降低副作用。我们利用富勒醇作为“组蛋白”,包裹了大量的 DOX,并使用 PEG-PLGA 作为“核被膜”,对“核小体”(富勒醇和 DOX 复合物)进行涂层以稳定复合物。值得注意的是,聚合物胶束中 DOX 的包封效率从约 5%提高到约 79%。更重要的是,仿生递药系统利用富勒醇的自由基清除能力显著降低了化学药物的副作用。这种新型药物输送设计方法为提高富勒醇在癌症治疗药物输送系统中的适用性提供了有用的见解。

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