Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
复制标题
多糖稳定的阿霉素共轭介孔磁性胶体纳米晶簇作为智能抗癌药物载体
DOI：
10.1002/smll.201200272
复制
发表时间：
2012-09-10
期刊：
影响因子：
13.3
通讯作者：
Wang, Changchun
中科院分区：
文献类型：
--
作者：
Li, Dian;Tang, Jing;Wang, Changchun
制备具有增强生物相容性和优异胶体稳定性的磁性纳米载体对于磁驱动药物递送的应用至关重要，这仍然是一个挑战。本文描述了一种合成琼脂糖稳定介孔磁性胶体纳米晶体团簇（mmcnc）的新方法；这些团簇具有高磁化强度、大表面积和孔隙体积、优异的胶体稳定性、增强的生物相容性和酸降解性。覆盖在磁性纳米晶体表面的琼脂糖羟基被乙烯基修饰，然后与巯基乙酰肼发生连锁反应，形成末端肼（CONHNH2）。然后，抗癌剂阿霉素（DOX）通过腙键与mmcnc结合。由此产生的腙是酸可切割的，从而提供ph敏感的药物释放能力。这种新型载体为构建新型磁驱动给药系统迈出了重要的一步。实验结果表明，DOX偶联mmcnc （mmcnc -DOX）在低pH下（肿瘤细胞：内溶酶体晚期pH为45，内溶酶体早期至晚期pH为56）的DOX释放率显著提高，而在中性pH下（血浆）几乎不释放DOX。MTT法测定的mmcnc - dox的细胞毒性显示出相当的抗肿瘤功效，但与游离药物相比，正常细胞系的细胞毒性较低，从而实现了减少与药物释放控制相关的正常组织副作用的目的。
Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (CONHNH2). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 45 in the late stage of endolysosome and pH 56 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release.