Biotinylated poly(amido)amine (PAMAM) dendrimers as carriers for drug delivery to ovarian cancer cells in vitro.
Biotinylated poly(amido)amine (PAMAM) dendrimers as carriers for drug delivery to ovarian cancer cells in vitro.
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发表时间：
2009-08
影响因子：
2
通讯作者：
V. Yellepeddi;Ajay Kumar;S. Palakurthi
中科院分区：
文献类型：
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作者：
V. Yellepeddi;Ajay Kumar;S. Palakurthi
背景技术生物素是一种必需的微量营养素，并且其在快速增殖的细胞例如癌细胞中的水平很高。我们假设聚（酰胺）胺（PAMAM）树枝状聚合物与生物素分子的合成可能有助于增强癌细胞的特异性摄取。材料和方法 PAMAM 树枝状大分子使用磺基-NHS-LC-生物素进行生物素化，并使用 1 H NMR 和基质辅助激光解吸电离飞行时间进行结构表征。通过荧光显微镜和流式细胞术测定卵巢癌（OVCAR-3）和人胚肾（HEK 293T）细胞中生物素-PAMAMG4的产生和细胞摄取机制。结果 与 HEK 293T 细胞相比，OVCAR-3 细胞对生物素-PAMAM 的细胞摄取显着更高 (p<0.05)。而游离生物素或秋水仙碱的存在显着降低了较低浓度（0.1 µM）生物素-PAMAMG4 的吸收程度。结果表明，生物素化-PAMAM 通过生物素受体介导的内吞作用和电荷介导的吸附内吞作用内化。 HEK 293T 细胞中生物素化的 PAMAMG4 的细胞毒性与亲本 PAMAM 树枝状聚合物相当。结论 生物素化的 PAMAM 树枝状聚合物在靶向药物递送方面显示出作为纳米载体的潜力。
BACKGROUND Biotin is an essential micronutrient and its levels are high in rapidly proliferating cells such as cancer cells. We hypothesized that the synthesis of poly (amido)amine (PAMAM) dendrimers with biotin molecules might contribute to enhanced cancer cell-specific uptake. MATERIALS AND METHODS PAMAM dendrimers were biotinylated using sulfo-NHS-LC-biotin and structural characterization was performed using 1H NMR and matrix assisted laser desorption ionization--time-of-flight. The effect of generation and the mechanism of cellular uptake of biotin-PAMAMG4 in ovarian cancer (OVCAR-3) and human embryonic kidney (HEK 293T) cells was determined by fluorescent microscopy and flow cytometry. RESULTS The cellular uptake of Biotin-PAMAM was significantly higher in the OVCAR-3 cells as compared to the HEK 293T cells (p<0.05). While the presence of either free biotin or colchicine significantly reduced the extent of uptake of biotin-PAMAMG4 at lower concentration (0.1 microM). The results demonstrated that the biotinylated-PAMAM was internalized by biotin receptor-mediated endocytosis and charge-mediated adsorptive endocytosis. The cytotoxicity of biotinylated-PAMAMG4 in the HEK 293T cells was comparable to that of the parent PAMAM dendrimers. CONCLUSION Biotinylated PAMAM dendrimers show potential as nanocarriers in targeted drug delivery.