Poly(PS-b-DMA) micelles for reactive oxygen species triggered drug release.
Poly(PS-b-DMA) micelles for reactive oxygen species triggered drug release.
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DOI：
10.1016/j.jconrel.2012.07.042
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发表时间：
2012-09-28
期刊：
影响因子：
--
通讯作者：
Duvall CL
中科院分区：
文献类型：
--
作者：
Gupta MK;Meyer TA;Nelson CE;Duvall CL
合成了一种新的胶束药物载体，由硫化丙烯（PS）和N，N-二甲基丙烯酰胺（聚（PS 74 − b-DMA 310））的二嵌段聚合物组成，其特征在于将疏水药物位点特异性释放到炎症部位。首先使用硫代酰基转移（TAGT）方法与RAFT链转移剂（CTA）4-氰基-4-（乙基硫烷基硫代羰基硫烷基）戊酸（CEP）聚合丙烯硫，并且使用可逆加成-断裂链转移（RAFT）将所得聚（PS 74-CEP）大分子CTA用于聚合DMA的第二聚合物嵌段。通过1H NMR光谱和凝胶渗透色谱法（GPC）确认了聚（PS 74 − b-DMA 310）二嵌段聚合物的形成。通过动态光散射（DLS）和透射电子显微镜（TEM）证实，聚（PS 74 − b-DMA 310）在水性介质中形成100 nm胶束。胶束加载模型药物尼罗红和二O被用来证明ROS依赖的药物释放机制，这些胶束处理后与过氧化氢（H2 O2），3-吗啉代异壬亚胺（SIN-1），和过氧亚硝酸盐。发现这些氧化剂氧化胶束PPS核心，使其更具亲水性，并引发胶束解体和货物释放。递送双负载有Förster共振能量转移（FRET）荧光团对DiI和DiO的聚（PS 74 − b-DMA 310）胶束用于证明由脂多糖（LPS）处理的RAW 264.7巨噬细胞产生的内源性氧化剂相对于未活化的巨噬细胞显著增加纳米载体内容物的释放。体外研究还表明，聚（PS 74 − b-DMA 310）胶束在广泛的浓度范围内具有细胞相容性。这些综合数据表明，使用TAGT和RAFT组合合成的聚（PS 74 − b-DMA 310）胶束具有向具有高水平氧化应激的组织进行位点特异性药物递送的显著潜力。
A new micelle drug carrier that consists of a diblock polymer of propylene sulfide (PS) and N,N-dimethylacrylamide (poly(PS74−b-DMA310)) has been synthesized and characterized for site-specific release of hydrophobic drugs to sites of inflammation. Propylene sulfide was first polymerized using a thioacyl group transfer (TAGT) method with the RAFT chain transfer agent (CTA) 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl) pentanoic acid (CEP), and the resultant poly(PS74−CEP) macro-CTA was used to polymerize a second polymer block of DMA using reversible addition-fragmentation chain transfer (RAFT). The formation of the poly(PS74−b-DMA310) diblock polymer was confirmed by 1H NMR spectra and gel permeation chromatography (GPC). poly(PS74−b-DMA310) formed 100 nm micelles in aqueous media as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Micelles loaded with the model drugs Nile red and DiO were used to demonstrate the ROS-dependent drug release mechanism of these micelles following treatment with hydrogen peroxide (H2O2), 3-morpholinosydnonimine (SIN-1), and peroxynitrite. These oxidants were found to oxidize the micelle PPS core, making it more hydrophilic and triggering micelle disassembly and cargo release. Delivery of poly(PS74−b-DMA310) micelles dual-loaded with the Förster Resonance Energy Transfer (FRET) fluorophore pair DiI and DiO was used to prove that endogenous oxidants generated by lipopolysaccharide (LPS)-treated RAW 264.7 macrophages significantly increased release of nanocarrier contents relative to macrophages that were not activated. In vitro studies also demonstrated that the poly(PS74−b-DMA310) micelles were cytocompatible across a broad range of concentrations. These combined data suggest that the poly(PS74−b-DMA310) micelles synthesized using a combination of TAGT and RAFT have significant potential for site-specific drug delivery to tissues with high levels of oxidative stress.
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DOI：
10.1016/j.jconrel.2008.10.004
发表时间：
2009-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Convertine AJ;Benoit DS;Duvall CL;Hoffman AS;Stayton PS
通讯作者：
Stayton PS
影响因子：
4.1
作者：
Emre, Yalin;Hurtaud, Corinne;Cassard-Doulcier, Anne-Marie
通讯作者：
Cassard-Doulcier, Anne-Marie
影响因子：
4.6
作者：
Ma, Ning;Li, Ying;Zhang, Xi
通讯作者：
Zhang, Xi
影响因子：
3.9
作者：
Jiang, Yugui;Wang, Yapei;Zhang, Xi
通讯作者：
Zhang, Xi
影响因子：
6.2
作者：
Convertine, A. J.;Diab, C.;Prieve, M.;Paschal, A.;Hoffman, A. S.;Johnson, P. H.;Stayton, P. S.
通讯作者：
Stayton, P. S.