Drug-Loaded and Superparamagnetic Iron Oxide Nanoparticle Surface-Embedded Amphiphilic Block Copolymer Micelles for Integrated Chemotherapeutic Drug Delivery and MR Imaging
Drug-Loaded and Superparamagnetic Iron Oxide Nanoparticle Surface-Embedded Amphiphilic Block Copolymer Micelles for Integrated Chemotherapeutic Drug Delivery and MR Imaging
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用于集成化疗药物输送和 MR 成像的载药超顺磁性氧化铁纳米颗粒表面嵌入两亲性嵌段共聚物胶束
DOI：
10.1021/la203992q
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发表时间：
2012-01-31
期刊：
影响因子：
3.9
通讯作者：
Liu, Shiyong
中科院分区：
文献类型：
--
作者：
Hu, Jinming;Qian, Yinfeng;Liu, Shiyong
我们报道了两亲性嵌段共聚物的有机/无机杂化胶束的制备，其具有化疗药物递送和磁共振（MR）成像对比增强的集成功能，其中疏水药物被物理地包裹在胶束核内，并且超顺磁性氧化铁（SPIO）纳米颗粒被稳定地嵌入在亲水性冠状物内。首先通过开环聚合（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分别为低聚乙二醇单甲基醚甲基丙烯酸酯和含叶酸基团。利用PCL-b-PGMA和PCL-b-P（OEGMA-co-FA）二嵌段共聚物的胶束核的疏水性和PGMA中1，2-二醇基团与SPIO纳米粒表面Fe原子的强亲和力，将模型疏水抗癌药物紫杉醇（PTX）和4 nm SPIO纳米粒分别负载到混合胶束的胶束核和亲水冠中.紫杉醇从混合胶束中的控制和持续释放，表现出类似于61%的包封药物（载量，8.5 w/w%）在类似于130 h的累积释放。与表面活性剂稳定的单一SPIO纳米颗粒（r（2）= 28.3 s（-1）mM（-1）Fe）相比，SPIO纳米颗粒在胶束冠内的聚集导致显著增强的T-2弛豫率（r（2）= 121.1 s（-1）mM（-1）Fe），这表明混合胶束可以作为具有改进性能的T-r加权MR成像对比增强剂。此外，还进行了在体MR成像的初步实验。这些结果表明，两亲性嵌段共聚物胶束表面嵌入SPIO纳米粒子的亲水冠，可以作为新一代的纳米平台集成靶向药物输送，控制释放，和疾病诊断功能。
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(epsilon-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 nanopartides. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of similar to 61% encapsulated drugs (loading content, 8.5 w/w%) over similar to 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-r-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.