PDF(Pubmed)
Abstract：
Dendrimers are potent nanocarriers in drug delivery systems because their structure can be precisely controlled. We previously reported that polyamidoamine (PAMAM) dendrimers that were modified with 1,2-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe), PAMAM-CHex-Phe, exhibited an effective association with various immune cells, including T-cells. In this study, we synthesized various carboxy-terminal Phe-modified dendrimers with different linkers using phthalic acid and linear dicarboxylic acids to determine the association of these dendrimers with Jurkat cells, a T-cell model. PAMAM-n-hexyl-Phe demonstrated the highest association with Jurkat T-cells. In addition, dendri-graft polylysine (DGL) with CHex and Phe, DGL-CHex-Phe, was synthesized, and its association with Jurkat cells was investigated. The association of DGL-CHex-Phe with T-cells was higher than that of PAMAM-CHex-Phe. However, it was insoluble in water and thus it is unsuitable as a drug carrier. Model drugs, such as protoporphyrin IX and paclitaxel, were loaded onto these dendrimers, and the most model drug molecules could be loaded into PAMAM-CHex-Phe. PTX-loaded PAMAM-CHex-Phe exhibited cytotoxicity against Jurkat cells at a similar level to free PTX. These results suggest that PAMAM-CHex-Phe exhibited both efficient T-cell association and drug loading properties.
摘要：
树枝状聚合物是药物递送系统中有效的纳米载体,因为它们的结构可以被精确控制。我们以前报道了用1,2-环己烷二羧酸（CHex）和苯丙氨酸（Phe）修饰的聚酰胺胺（PAMAM）树枝状聚合物，PAMAM-CHex-Phe,表现出与各种免疫细胞的有效关联，包括T细胞。在这项研究中,我们使用邻苯二甲酸和线性二羧酸合成了具有不同连接体的各种羧基末端Phe修饰的树枝状聚合物，以确定这些树枝状聚合物与Jurkat细胞的缔合，T细胞模型.PAMAM-正己基-Phe与JurkatT细胞的相关性最高。此外,树枝状接枝聚赖氨酸（DGL）与CHex和Phe，DGL-CHex-Phe,是合成的，并对其与Jurkat细胞的关联进行了研究。DGL-CHex-Phe与T细胞的相关性高于PAMAM-CHex-Phe。然而,它不溶于水，因此不适合作为药物载体。模型药物，如原卟啉IX和紫杉醇，被装载到这些树枝状聚合物上，大多数模型药物分子可以装载到PAMAM-CHex-Phe中。负载PTX的PAMAM-CHex-Phe表现出与游离PTX相似水平的对Jurkat细胞的细胞毒性。这些结果表明PAMAM-CHex-Phe表现出有效的T细胞缔合和药物负载特性。
