Hollow-core magnetic colloidal nanocrystal clusters with ligand-exchanged surface modification as delivery vehicles for targeted and stimuli-responsive drug release.
Hollow-core magnetic colloidal nanocrystal clusters with ligand-exchanged surface modification as delivery vehicles for targeted and stimuli-responsive drug release.
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DOI：
10.1002/chem.201202249
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发表时间：
2012-12
期刊：
影响因子：
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通讯作者：
D. Li;Jingyou Tang;Jia Guo;Shilong Wang;D. Chaudhary;Changchun Wang
中科院分区：
文献类型：
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作者：
D. Li;Jingyou Tang;Jia Guo;Shilong Wang;D. Chaudhary;Changchun Wang
具有明确结构、高磁响应、优异的胶体稳定性和生物相容性的分级磁性纳米材料的制造在药物递送系统中受到高度追捧。本文采用溶剂热一锅法合成了一种具有多孔壳和可调空腔的空心磁性胶体团簇（HMCNC）。其新奇在于通过分别控制柠檬酸钠和水的进料，中空腔室和壳内孔结构的“可调谐性”。此外，通过使用配体交换法，叶酸修饰的聚（丙烯酸）固定在HMCCs的表面，以创建叶酸靶向HMCCs（叶酸-HMCCs），这赋予了他们优异的胶体稳定性，pH敏感性，更重要的是，叶酸受体的靶向能力。这些组装体在血浆溶液中表现出优异的胶体稳定性。以阿霉素（DOX）为模型药物，将其负载于叶酸-HMCCNCs中空核内，药物释放实验证明叶酸-HMCCNCs-DOX具有pH依赖性释放行为。叶酸-HMCCs-DOX组合物对HeLa细胞的细胞毒性也比游离阿霉素强。此外，叶酸-HMCNCs-DOX除了对HeLa细胞的增强的细胞毒性外，还显示出快速的细胞摄取。实验结果证实，合成的叶酸-HMCNC是智能纳米载体，这是由于其改善的叶酸受体靶向能力，也是因为其组合的pH和磁刺激响应用于药物递送。
The fabrication of hierarchical magnetic nanomaterials with well-defined structure, high magnetic response, excellent colloidal stability, and biocompatibility is highly sought after for drug-delivery systems. Herein, a new kind of hollow-core magnetic colloidal nanocrystal cluster (HMCNC) with porous shell and tunable hollow chamber is synthesized by a one-pot solvothermal process. Its novelty lies in the "tunability" of the hollow chamber and of the pore structure within the shell through controlled feeding of sodium citrate and water, respectively. Furthermore, by using the ligand-exchange method, folate-modified poly(acrylic acid) was immobilized on the surface of HMCNCs to create folate-targeted HMCNCs (folate-HMCNCs), which endowed them with excellent colloidal stability, pH sensitivity, and, more importantly, folate receptor-targeting ability. These assemblages exhibited excellent colloidal stability in plasma solution. Doxorubicin (DOX), as a model anticancer agent, was loaded within the hollow core of these folate-HMCNCs (folate-HMCNCs-DOX), and drug-release experiments proved that the folate-HMCNCs-DOX demonstrated pH-dependent release behavior. The folate-HMCNCs-DOX assemblages also exhibited higher potent cytotoxicity to HeLa cells than free doxorubicin. Moreover, folate-HMCNCs-DOX showed rapid cell uptake apart from the enhanced cytotoxicity to HeLa cells. Experimental results confirmed that the synthesized folate-HMCNCs are smart nanovehicles as a result of their improved folate receptor-targeting abilities and also because of their combined pH- and magnetic-stimuli response for applications in drug delivery.