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一种具有治疗潜力的生物相容氧化触发载体聚合物。

A biocompatible oxidation-triggered carrier polymer with potential in therapeutics.

机构信息

Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.

出版信息

J Am Chem Soc. 2011 Feb 2;133(4):756-8. doi: 10.1021/ja110468v.

Abstract

Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its hydroxyls with arylboronic esters to make it soluble in common organic solvents, allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX) carrier microparticles. These particles were found to release their payload with a half-life of 36 min at 1 mM H2O2, which can be compared with a half-life of greater than 1 week in the absence of H2O2. When used in a model vaccine application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the presentation to CD8+ T-cells 27-fold relative to OVA encapsulated in a classical vehicle not sensitive to oxidation. No presentation was observed from cells incubated with unencapsulated OVA. Additionally, Oxi-DEX was found to be nontoxic in preliminary in vitro cytotoxicity assays. Because it is easy to prepare, sensitive to biological oxidation, and biocompatible, this material may represent an attractive new platform for selective delivery applications.

摘要

葡聚糖是一种水溶性、生物相容的葡萄糖聚合物,其羟基被芳基硼酸酯修饰,使其可溶于常见有机溶剂,从而可以方便地制备氧化敏感的葡聚糖(Oxi-DEX)载体微球。研究发现,这些颗粒在 1mM H2O2 下的半衰期为 36 分钟,而在没有 H2O2 的情况下半衰期大于 1 周。当用于模型疫苗应用时,负载卵清蛋白(OVA)的 Oxi-DEX 颗粒与对氧化不敏感的经典载体包封的 OVA 相比,向 CD8+T 细胞的呈递增加了 27 倍。与未包封的 OVA 孵育的细胞没有观察到呈递。此外,初步的体外细胞毒性试验发现 Oxi-DEX 没有毒性。由于其易于制备、对生物氧化敏感且生物相容,因此该材料可能代表一种有吸引力的新型选择性递药平台。

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