Design of Core-Shell-Type Nanoparticles Carrying Stable Radicals in the Core
Design of Core-Shell-Type Nanoparticles Carrying Stable Radicals in the Core
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DOI：
10.1021/bm801278n
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发表时间：
2009-03-01
影响因子：
6.2
通讯作者：
Nagasaki, Yukio
中科院分区：
文献类型：
--
作者：
Yoshitomi, Toru;Miyamoto, Daisuke;Nagasaki, Yukio
利用自组装核壳型聚合物胶束技术，制备了核内具有稳定自由基、外围具有活性基团的高性能纳米粒子。以3，3-二乙氧基丙醇钾为引发剂，环氧乙烷（EO）进行阴离子开环聚合，然后与甲磺酰氯进行甲磺酰化反应，得到缩醛-聚乙二醇甲磺酸酯（acetal-PEG-Ms; 1）。化合物1与O-乙基二硫代碳酸钾反应，然后用正丙胺处理，以高选择性和定量的方式获得含有硫烷基和缩醛端基的异双官能PEG衍生物（缩醛-PEG-SH）（2）。以2为调聚剂，通过氯甲基苯乙烯（CMS）的自由基调聚反应，合成了聚乙二醇-聚氯甲基苯乙烯嵌段共聚物（3）。嵌段共聚物（3）的PCMS链段中的氯甲基通过3与4-氨基-TEMPO的胺化定量转化为2，2，6，6-四甲基哌啶氧基（TEMPO），以获得含有克里思部分的缩醛-PEG-b-PCMS（4）。在水溶液中，透析法制备的4种纳米粒子均为核壳结构，累积平均粒径约为40 nm，发射出强烈的电子顺磁共振（EPR）信号。在纳米颗粒的核心克里思自由基显示还原阻力，即使在3.5 mM的抗坏血酸的存在下。这意味着这些纳米颗粒有望成为可在体内使用的高性能生物纳米颗粒。
Utilizing the self-assembled core-shell-type polymeric micelle technique, high-performance nanoparticles possessing stable radicals in the core and reactive groups on the periphery were prepared. The anionic ring-opening polymerization of ethylene oxide (EO) was carried out using potassium 3,3-diethoxypropanolate as an initiator, followed by mesylation with methanesulfonyl chloride to obtain acetal-poly(ethylene glycol)methanesulfonate (acetal-PEG-Ms; 1). Compound 1 was reacted with potassium O-ethyldithiocarbonate, followed by treatment with n-propylamine to obtain heterobifunctional PEG derivatives containing both sulfanyl and acetal terminal groups (acetal-PEG-SH) (2) in a highly selective and quantitative manner. Poly(ethylene glycol)-block-poly(chloromethylstyrene) (acetal-PEG-b-PCMS) (3) was synthesized by the free-radical telomerization of chloromethylstyrene (CMS) using 2 as a telogen. The chloromethyl groups in the PCMS segment of the block copolymer (3) were quantitatively convened to 2,2,6,6-tetramethylpiperidinyloxys (TEMPOs) via the amination of 3 with 4-amino-TEMPO to obtain acetal-PEG-b-PCMS containing TEMPO moieties (4). The obtained 4 formed core-shell-type nanoparticles in aqueous media when subjected to the dialysis method: the cumulant average diameter of the nanoparticles was about 40 nm, and the nanoparticles emitted intense electron paramagnetic resonance (EPR) signals. The TEMPO radicals in the core of the nanoparticles showed reduction resistance even in the presence of 3.5 mM ascorbic acid. This means that these nanoparticles are anticipated as high-performance bionanoparticles that can be used in vivo.