Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy
Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy
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DOI：
10.1021/jm0401863
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发表时间：
2005-09-22
影响因子：
7.3
通讯作者：
Baker, JR
中科院分区：
文献类型：
--
作者：
Majoros, IJ;Thomas, TP;Baker, JR
使用聚酰胺胺（PAMAM）树枝状聚合物作为载体，设计并合成了多功能癌症治疗纳米器件。第 5 代 (G5) PAMAM 树枝状聚合物的部分乙酰化用于中和部分伯氨基，在异硫氰酸荧光素 (FITC)（在二甲基亚砜 (DMSO) 中）的缀合反应期间提供增强的树枝状聚合物溶解度，并防止递送过程中的非特异性靶向相互作用（体外和体内）。剩余的非乙酰化伯氨基用于缀合功能分子异硫氰酸荧光素（FITC，一种显像剂）、叶酸（FA，针对特定癌细胞上过度表达的叶酸受体）和甲氨蝶呤（MTX，化疗药物）。适当的控制纳米器件也已被合成。 G5 PAMAM 树枝状聚合物的分子量和伯氨基数量通过凝胶渗透色谱 (GPC) 和电位滴定法测定，用于随后的缀合反应的化学计量设计。此外，树枝状聚合物缀合物通过多种分析方法进行了表征，包括 GPC、核磁共振光谱 (NMR)、高效液相色谱 (HPLC) 和紫外光谱。完全表征的纳米装置可用于将化疗剂和显像剂靶向输送至特定癌细胞。在这里，我们对之前报道的这种材料的合成进行了更广泛的研究，并针对放大合成和临床试验进行了改进。
Multifunctional cancer therapeutic nanodevices have been designed and synthesized using the poly(amidoamine) (PAMAM) dendrimer as a carrier. Partial acetylation of the generation 5 (G5) PAMAM dendrimer was utilized to neutralize a fraction of the primary amino groups, provide enhanced solubility of the dendrimer during the conjugation reaction of fluorescein isothiocyanate (FITC) (in dimethyl sulfoxide (DMSO)), and prevent nonspecific targeting interactions (in vitro and in vivo) during delivery. The remaining nonacetylated primary amino groups were utilized for conjugation of the functional molecules fluorescein isothiocyanate (FITC, an imaging agent), folic acid (FA, targets overexpressed folate receptors on specific cancer cells), and methotrexate (MTX, chemotherapeutic drug). The appropriate control nanodevices have been synthesized as well. The G5 PAMAM dendrimer molecular weight and number of primary amino groups were determined by gel permeation chromatography (GPC) and potentiometric titration for stoichiometric design of ensuing conjugation reactions. Additionally, dendrimer conjugates were characterized by multiple analytical methods including GPC, nuclear magnetic resonance spectroscopy (NMR), high performance liquid chromatography (HPLC), and UV spectroscopy. The fully characterized nanodevices can be used for the targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. Here, we present a more extensive investigation of our previously reported synthesis of this material with improvements directed toward scale-up synthesis and clinical trials.