Doxorubicin conjugated gold nanoparticles as water-soluble and pH-responsive anticancer drug nanocarriers
Doxorubicin conjugated gold nanoparticles as water-soluble and pH-responsive anticancer drug nanocarriers
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DOI：
10.1039/b914071a
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Gong, Shaoqin
中科院分区：
文献类型：
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作者：
Aryal, Santosh;Grailer, Jamison J.;Gong, Shaoqin
水溶性多柔比星（DOX）共轭金纳米粒子（DOX共轭金纳米粒子）具有显著的ph响应药物释放谱，并在本研究中进行了表征。硫代甲氧基聚乙二醇（MPEG-SH）和巯基乙酸甲酯（MTG）以等摩尔比稳定Au NPs。将抗癌药物DOX以肼为连接剂偶联到巯基稳定的Au NPs的MTG片段上。DOX分子和巯基稳定的Au NPs的MTG片段之间形成的腙键是酸可切割的，从而提供了强ph响应的药物释放谱。附着在Au NPs上的MPEG片段使Au NPs在水介质中具有良好的溶解度和稳定性，同时可能延长循环时间。DOX负荷水平确定为23%。DOX共轭Au NPs在酸性介质（即pH 5.3）中的DOX释放率显著高于生理条件（即pH 7.4）。在DOX偶联Au NPs溶液中孵育28小时后，在4T1肿瘤细胞的核周区域和细胞核中都发现了DOX偶联Au NPs和/或从中释放的DOX。这些新型DOX偶联Au NPs具有增强CT成像对比度和促进光热癌症治疗的潜力，同时将抗癌药物输送到靶点。
Water-soluble, doxorubicin (DOX) conjugated gold nanoparticles ( DOX conjugated Au NPs) exhibiting a significant pH-responsive drug release profile have been prepared and characterized in this study. The Au NPs were stabilized by thiolated methoxy polyethylene glycol (MPEG-SH) and methyl thioglycolate (MTG) at an equal molar ratio. The anticancer drug DOX was conjugated to the MTG segments of the thiol-stabilized Au NPs using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the MTG segments of the thiol-stabilized Au NPs are acid cleavable, thereby providing a strong pH-responsive drug release profile. The MPEG segments attached to the Au NPs provide the Au NPs with excellent solubility and stability in an aqueous medium while potentially enhancing the circulation time. The DOX loading level was determined to be 23 wt.%. The DOX release rate from the DOX conjugated Au NPs in an acid medium (i.e., pH 5.3) was dramatically higher than that in physiological conditions (i.e., pH 7.4). The DOX conjugated Au NPs and/or the DOX released from them were found both at the perinuclear regions and the nuclei of 4T1 tumor cells after incubation in a DOX conjugated Au NPs solution for 28 h. These novel DOX conjugated Au NPs have the potential to simultaneously enhance CT imaging contrast and facilitate photothermal cancer therapy while delivering anticancer drugs to their target sites.