CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
Langmuir. 2012 Jan 31;28(4):2073-82. doi: 10.1021/la203992q. Epub 2011 Nov 11.
We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic block copolymers physically encapsulated with hydrophobic drugs within micellar cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles within hydrophilic coronas, which possess integrated functions of chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast enhancement. Poly(ε-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b-PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at first by combining ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and post- modification techniques, where OEGMA and FA are oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX), and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b-P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms at the surface of SPIO nanoparticles. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of ~61% encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe), the clustering of SPIO nanoparticles within micellar coronas led to considerably enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved performance. Moreover, preliminary experiments of in vivo MR imaging were also conducted. These results indicate that amphiphilic block copolymer micelles surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a new generation of nanoplatform integrating targeted drug delivery, controlled release, and disease diagnostic functions.
我们报告了一种有机/无机杂化胶束的制备方法，该胶束由两亲性嵌段共聚物物理包裹疏水性药物形成胶束内核，并在亲水性冠层内稳定嵌入超顺磁氧化铁（SPIO）纳米粒子，具有化疗药物递送和磁共振（MR）成像对比增强的综合功能。首先，通过结合开环聚合（ROP）、原子转移自由基聚合（ATRP）和后修饰技术合成了聚（ε-己内酯）-b-聚（甘油单甲基丙烯酸酯）（PCL-b-PGMA）和 PCL-b-P（OEGMA-co-FA）两亲性嵌段共聚物，其中 OEGMA 和 FA 分别为聚乙二醇单甲基醚甲基丙烯酸酯和叶酸部分。然后，将模型疏水性抗癌药物紫杉醇（PTX）和 4nm 的 SPIO 纳米粒子分别负载到由 PCL-b-PGMA 和 PCL-b-P（OEGMA-co-FA）两嵌段共聚物制备的混合胶束的胶束内核和亲水性冠层中，这是利用了胶束内核的疏水性以及 PGMA 中的 1,2-二醇基团和 SPIO 纳米粒子表面的 Fe 原子之间的强亲和力。从混合胶束中实现了对 PTX 的控制和持续释放，在 130 小时内实现了约 61%的包裹药物的累积释放（负载量为 8.5w/w%）。与表面活性剂稳定的单 SPIO 纳米粒子（r2=28.3s-1mM-1Fe）相比，SPIO 纳米粒子在胶束冠层内的聚集导致 T2弛豫率（r2=121.1s-1mM-1Fe）显著提高，表明杂化胶束可用作具有改进性能的 T2加权磁共振成像对比增强剂。此外，还进行了体内磁共振成像的初步实验。这些结果表明，在亲水性冠层内嵌入 SPIO 纳米粒子的两亲性嵌段共聚物胶束可以作为一种新型纳米平台，整合靶向药物递送、控制释放和疾病诊断功能。
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