Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor
Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor
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DOI：
10.1023/a:1020398624602
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发表时间：
2002-09-01
影响因子：
3.7
通讯作者：
Baker, JR
中科院分区：
文献类型：
--
作者：
Quintana, A;Raczka, E;Baker, JR
目的.我们试图开发纳米级药物递送材料，其允许靶向细胞内递送，同时具有用于跟踪材料摄取的成像能力。设计并合成了一种通过叶酸受体靶向肿瘤细胞的复杂纳米器件。该设备是基于乙二胺核心聚酰胺胺树枝状聚合物的第5代。叶酸，荧光素，甲氨蝶呤共价连接到表面，以提供靶向，成像和细胞内药物输送能力。分子模拟确定了最佳的树枝状聚合物表面改性的设备的功能，并建议表面改性，提高了目标。合成了三种纳米器件。KB细胞中的实验靶向数据证实了特异性和高选择性结合的建模预测。靶向给药使细胞对甲氨蝶呤的细胞毒性反应比游离药物提高了100倍。这些结果证明了设计和生产基于聚合物的纳米器件用于药物、成像剂和其他材料的细胞内靶向的能力。
Purpose. We sought to develop nanoscale drug delivery materials that would allow targeted intracellular delivery while having an imaging capability for tracking uptake of the material. A complex nanodevice was designed and synthesized that targets tumor cells through the folate receptor.Methods. The device is based on an ethylenediamine core polyamidoamine dendrimer of generation 5. Folic acid, fluorescein, and methotrexate were covalently attached to the surface to provide targeting, imaging, and intracellular drug delivery capabilities. Molecular modeling determined the optimal dendrimer surface modification for the function of the device and suggested a surface modification that improved targeting.Results. Three nanodevices were synthesized. Experimental targeting data in KB cells confirmed the modeling predictions of specific and highly selective binding. Targeted delivery improved the cytotoxic response of the cells to methotrexate 100-fold over free drug.Conclusions. These results demonstrate the ability to design and produce polymer-based nanodevices for the intracellular targeting of drugs, imaging agents, and other materials.