19F- and fluorescently labeled micelles as nanoscopic assemblies for chemotherapeutic delivery.
19F- and fluorescently labeled micelles as nanoscopic assemblies for chemotherapeutic delivery.
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DOI：
10.1021/bc800396h
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发表时间：
2008-12
影响因子：
4.7
通讯作者：
Wooley, Karen L.
中科院分区：
文献类型：
--
作者：
Du, Wenjun;Xu, Zhiqiang;Nystroem, Andreas M.;Zhang, Ke;Leonard, Jeffrey R.;Wooley, Karen L.
来自两亲星形嵌段共聚物的胶束具有疏水性超支化核心和两亲含氟聚合物臂，被构建为药物递送剂组件。由4-氯甲基苯乙烯与丙烯酸十二烷基酯，然后甲基丙烯酸1,1,1-三氟乙酯与丙烯酸叔丁酯连续共聚，然后酸解释放出亲水性丙烯酸残基，构建了一系列聚合物结构。这些结构用级联蓝标记作为荧光报告基团。该系列材料的主要区别在于甲基丙烯酸 1,1,1-三氟乙酯与丙烯酸单元的比例，从而在氟负载量和疏水性/亲水性平衡方面产生差异。使用阿霉素 (DOX) 作为治疗剂来研究这些胶束结构在 U87-MG-EGFRvIII-CBR 细胞系上的负载、释放和细胞毒性。胶束的 TEM 测量直径为 5-9 nm，DLS 测量的流体动力学直径为 20-30 nm，负载能力约为 100 nm。 4 wt% DOX。通过 MTT 测定，负载 DOX 的胶束表现出有效的细胞毒性，在 1.0 μg/mL 有效 DOX 浓度下，细胞活力为 60-25%，具体取决于聚合物成分。这些细胞活力值与游离 DOX 相当，表明货物有效释放并递送至细胞核，这通过细胞荧光显微镜进一步证实。 19F-NMR 光谱表明胶束表面可用的三氟乙酯键部分降解，这可能加速了 DOX 的释放。 19F-NMR 光谱也用于确认和量化胶束的细胞摄取。这些双荧光和 19F 标记的化学功能胶束可用于多种应用，例如细胞标记、成像和治疗递送。
Micelles from amphiphilic star-block copolymers, having a hydrophobic hyperbranched core and amphiphilic fluoropolymer arms, were constructed as drug delivery-agent assemblies. A series of polymer structures was constructed from consecutive copolymerizations of 4-chloromethylstyrene with dodecyl acrylate and then 1,1,1-trifluoroethyl methacrylate with tert-butyl acrylate, followed by acidolysis to release the hydrophilic acrylic acid residues. These structures were labeled with cascade blue as a fluorescence reporter. The series of materials differed primarily in the ratio of 1,1,1-trifluoroethyl methacrylate to acrylic acid units, to give differences in fluorine loading and hydrophobicity/hydrophilicity balance. Doxorubicin (DOX) was used as a therapeutic to study the loading, release and cytotoxicity of these micellar constructs on an U87-MG-EGFRvIII-CBR cell line. The micelles, with TEM-measured diameters ranging from 5–9 nm and DLS-measured hydrodynamic diameters from 20–30 nm, had loading capacities of ca. 4 wt% of DOX. The DOX-loaded micelles exhibited potent cytotoxicity with cell viabilities of 60-25% at 1.0 μg/mL effective DOX concentrations, depending upon the polymer composition, as determined by MTT assays. These cell viability values are comparable to that of free DOX, suggesting an effective release of the cargo and delivery to the cell nuclei, which was further confirmed by fluorescence microscopy of the cells. 19F-NMR spectroscopy indicated a partial degradation of the surface-available trifluoroethyl ester linkages of the micelles, which may have accelerated the release of DOX. 19F-NMR spectroscopy was also employed to confirm and to quantify the cell uptake of the micelles. These dual fluorescent- and 19F-labeled and chemically-functional micelles may be used potentially in a variety of applications, such as cell labeling, imaging, and therapeutic delivery.
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影响因子：
6.2
作者：
Du, Wenjun;Nystrom, Andreas M.;Zhang, Lei;Powell, Kenya T.;Li, Yali;Cheng, Chong;Wickline, Samuel A.;Wooley, Karen L.
通讯作者：
Wooley, Karen L.
影响因子：
6.2
作者：
Sun, Guorong;Hagooly, Aviv;Welch, Michael J.
通讯作者：
Welch, Michael J.
影响因子：
20.1
作者：
Uwatoku, T;Shimokawa, H;Takeshita, A
通讯作者：
Takeshita, A
影响因子：
10.8
作者：
Nasongkla, Norased;Bey, Erik;Gao, Jinming
通讯作者：
Gao, Jinming
影响因子：
56.9
作者：
Dubertret, B;Skourides, P;Libchaber, A
通讯作者：
Libchaber, A