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通过原子转移自由基聚合制备的可生物降解纳米凝胶作为潜在药物递送载体:合成、生物降解、体外释放及生物共轭

Biodegradable nanogels prepared by atom transfer radical polymerization as potential drug delivery carriers: synthesis, biodegradation, in vitro release, and bioconjugation.

作者信息

Oh Jung Kwon, Siegwart Daniel J, Lee Hyung-il, Sherwood Gizelle, Peteanu Linda, Hollinger Jeffrey O, Kataoka Kazunori, Matyjaszewski Krzysztof

机构信息

Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.

出版信息

J Am Chem Soc. 2007 May 9;129(18):5939-45. doi: 10.1021/ja069150l. Epub 2007 Apr 18.

Abstract

Stable biodegradable nanogels cross-linked with disulfide linkages were prepared by inverse miniemulsion atom transfer radical polymerization (ATRP). These nanogels could be used for targeted drug delivery scaffolds for biomedical applications. The nanogels had a uniformly cross-linked network, which can improve control over the release of encapsulated agents, and the nanogels biodegraded into water-soluble polymers in the presence of a biocompatible glutathione tripeptide, which is commonly found in cells. The biodegradation of nanogels can trigger the release of encapsulated molecules including rhodamine 6G, a fluorescent dye, and Doxorubicin (Dox), an anticancer drug, as well as facilitate the removal of empty vehicles. Results obtained from optical fluorescence microscope images and live/dead cytotoxicity assays of HeLa cancer cells suggested that the released Dox molecules penetrated cell membranes and therefore could suppress the growth of cancer cells. Further, OH-functionalized nanogels were prepared to demonstrate facile applicability toward bioconjugation with biotin. The number of biotin molecules in each nanogel was determined to be 142,000, and the formation of bioconjugates of nanogels with avidin was confirmed using optical fluorescence microscopy.

摘要

通过反相微乳液原子转移自由基聚合(ATRP)制备了与二硫键交联的稳定可生物降解纳米凝胶。这些纳米凝胶可用于生物医学应用的靶向药物递送支架。纳米凝胶具有均匀交联的网络,这可以改善对包封剂释放的控制,并且纳米凝胶在细胞中常见的生物相容性谷胱甘肽三肽存在下可生物降解为水溶性聚合物。纳米凝胶的生物降解可以触发包括荧光染料罗丹明6G和抗癌药物阿霉素(Dox)在内的包封分子的释放,以及促进空载体的去除。从光学荧光显微镜图像和HeLa癌细胞的活/死细胞毒性试验获得的结果表明,释放的Dox分子穿透细胞膜,因此可以抑制癌细胞的生长。此外,制备了OH功能化的纳米凝胶,以证明其对与生物素进行生物共轭的简便适用性。测定每个纳米凝胶中生物素分子的数量为142,000,并使用光学荧光显微镜确认了纳米凝胶与抗生物素蛋白生物共轭物的形成。

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