PAMAM dendrimer-based multifunctional conjugate for cancer therapy: Synthesis, characterization, and functionality
PAMAM dendrimer-based multifunctional conjugate for cancer therapy: Synthesis, characterization, and functionality
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DOI：
10.1021/bm0506142
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发表时间：
2006-02-01
影响因子：
6.2
通讯作者：
Baker, JR
中科院分区：
文献类型：
--
作者：
Majoros, IJ;Myc, A;Baker, JR
设计并合成了基于聚酰胺-胺（PAMAM）树状大分子的多功能肿瘤治疗缀合物。第5代（G5）PAMAM树枝状聚合物表面上的伯氨基通过部分乙酰化被中和，从而提高树枝状聚合物的溶解度（与FITC（异硫氰酸荧光素）结合），并防止递送期间的非特异性靶向相互作用（体外和体内）。功能分子异硫氰酸荧光素（FITC，一种显像剂）、叶酸（FA，靶向特定癌细胞上过表达的叶酸受体）和紫杉醇（紫杉醇，一种化疗药物）与剩余的非乙酰化伯氨基结合。还合成了适当的对照树枝状聚合物缀合物。G5 PAMAM树枝状聚合物及其纳米级缀合物的表征，包括伯胺基团的分子量和数目，已经通过多种分析方法如凝胶渗透色谱法（GPC）、核磁共振光谱法（NMR）、电位滴定法、高效液相色谱法（HPLC）和UV光谱法确定。这些多功能树枝状聚合物缀合物已经在体外测试用于将化疗剂和成像剂靶向递送至特定癌细胞。我们在这里提出的合成，表征，和这些树枝状大分子共轭物的功能。
Poly(amidoamine) (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized. The primary amino groups on the surface of the generation 5 (G5) PAMAM dendrimer were neutralized through partial acetylation, providing enhanced solubility of the dendrimer (in conjugation of FITC (fluorescein isothiocyanate)) and preventing nonspecific targeting interactions (in vitro and in vivo) during delivery. The functional molecules fluorescein isothiocyanate (FITC, an imaging agent), folic acid (FA, targets overexpressed folate receptors on specific cancer cells), and paclitaxel (taxol, a chemotherapeutic drug) were conjugated to the remaining nonacetylated primary amino groups. The appropriate control dendrimer conjugates have been synthesized as well. Characterization of the G5 PAMAM dendrimer and its nanosize conjugates, including the molecular weight and number of primary amine groups, has been determined by multiple analytical methods such as gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR), potentiometric titration, high-performance liquid chromatography (HPLC), and UV spectroscopy. These multifunctional dendrimer conjugates have been tested in vitro for targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. We present here the synthesis, characterization, and functionality of these dendrimer conjugates.