Shiba Hiroya, Hirose Tomoka, Fu Yunshen, Michigami Masataka, Fujii Ikuo, Nakase Ikuhiko, Matsumoto Akikazu, Kojima Chie
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan.
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan.
Pharmaceutics. 2023 Mar 9;15(3):888. doi: 10.3390/pharmaceutics15030888.
T cells play important roles in various immune reactions, and their activation is necessary for cancer immunotherapy. Previously, we showed that polyamidoamine (PAMAM) dendrimers modified with 1,2-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe) underwent effective uptake by various immune cells, including T cells and their subsets. In this study, we synthesized various carboxy-terminal dendrimers modified with different bound numbers of Phe and investigated the association of these dendrimers with T cells to evaluate the influence of terminal Phe density. Carboxy-terminal dendrimers conjugating Phe at more than half of the termini exhibited a higher association with T cells and other immune cells. The carboxy-terminal Phe-modified dendrimers at 75% Phe density tended to exhibit the highest association with T cells and other immune cells, which was related to their association with liposomes. A model drug, protoporphyrin IX (PpIX), was encapsulated into carboxy-terminal Phe-modified dendrimers, which were then used for drug delivery into T cells. Our results suggest the carboxy-terminal Phe-modified dendrimers are useful for delivery into T cells.
T细胞在各种免疫反应中发挥着重要作用，其激活对于癌症免疫治疗是必要的。此前，我们表明用1,2 - 环己烷二羧酸（CHex）和苯丙氨酸（Phe）修饰的聚酰胺胺（PAMAM）树枝状大分子能被包括T细胞及其亚群在内的各种免疫细胞有效摄取。在本研究中，我们合成了用不同数量的Phe修饰的各种羧基末端树枝状大分子，并研究了这些树枝状大分子与T细胞的关联，以评估末端Phe密度的影响。在超过一半的末端连接有Phe的羧基末端树枝状大分子与T细胞和其他免疫细胞表现出更高的关联性。Phe密度为75%的羧基末端Phe修饰树枝状大分子往往与T细胞和其他免疫细胞表现出最高的关联性，这与其与脂质体的关联性有关。将一种模型药物原卟啉IX（PpIX）包封到羧基末端Phe修饰的树枝状大分子中，然后用于将药物递送至T细胞。我们的结果表明羧基末端Phe修饰的树枝状大分子可用于递送至T细胞。
