Folate and Folate-PEG-PAMAM Dendrimers: Synthesis, Characterization, and Targeted Anticancer Drug Delivery Potential in Tumor Bearing Mice
Folate and Folate-PEG-PAMAM Dendrimers: Synthesis, Characterization, and Targeted Anticancer Drug Delivery Potential in Tumor Bearing Mice
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DOI：
10.1021/bc800125u
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发表时间：
2008-11-01
影响因子：
4.7
通讯作者：
Jain, Narendra K.
中科院分区：
文献类型：
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作者：
Singh, Prateek;Gupta, Umesh;Jain, Narendra K.
配体介导的药物靶向尤其是抗癌药物递送是一种有效的方法。由于独特的表面拓扑结构，树枝状聚合物可以成为这种情况下的选择。在本研究中，合成了第四代PAMAM（聚酰胺胺）树枝状聚合物，并通过红外（IR）、核磁共振（NMR）、电喷雾电离（ESI）质谱和透射电子显微镜（TEM）技术进行了表征。树突表面上存在的伯胺通过叶酸和叶酸-PEG（聚乙二醇）-NHS（N-羟基琥珀酰亚胺）缀合物进行缀合。通过使用 KB 细胞培养物诱导小鼠肿瘤。使用 5-FU（5-氟尿嘧啶）在荷瘤小鼠中评估制备的树突状缀合物的抗癌药物递送潜力。大约 31% 的 5-FU 负载在叶酸-PEG-树突状缀合物中。结果表明，与非聚乙二醇化制剂相比，叶酸-PEG-树枝状大分子缀合物在肿瘤靶向方面显着安全有效。通过 PEG-叶酸剪裁树枝状大分子可降低溶血毒性，从而实现持续的药物释放模式以及在肿瘤区域的最高积累。
Ligand-mediated targeting of drugs especially in anticancer drug delivery is an effective approach. Dendrimers, due to unique surface topologies, can be a choice in this context. In the present study, PAMAM (polyamidoamine) dendrimers up to fourth generation were synthesized and characterized through infrared (IR), nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectrometric, and transmission electron microscopic (TEM) techniques. Primary amines present on the dendritic surface were conjugated through folic acid and folic acid-PEG (poly(ethylene glycol))-NHS (N-hydroxysuccinimide) conjugates. Tumor in mice was induced through the use of KB cell culture. Prepared dendritic conjugates were evaluated for the anticancer drug delivery potential using 5-FU (5-fluorouracil) in tumor-bearing mice. Approximately 31% of 5-FU was loaded in folate-PEG-dendritic conjugates. Results indicated that folate-PEG-dendrimer conjugate was significantly safe and effective in tumor targeting compared to a non-PEGylated formulation. Tailoring of dendrimers via PEG-folic acid reduced hemolytic toxicity, which led to a sustained drug release pattern as well as highest accumulation in the tumor area.