Issue 14, 2022

Carboxy-terminal dendrimers with phenylalanine for a pH-sensitive delivery system into immune cells including T cells

Abstract

Although T cells play important roles in various immune reactions, there are only a few reports on delivery systems into T cells. Our previous study showed that carboxy-terminal phenylalanine (Phe)-modified polyamidoamine (PAMAM) dendrimers have both temperature- and pH-sensitive properties, which are affected by the chemical structure. The self-assembled structures of Phe, observed in phenylketonuria, enhance the protein aggregation, the association with the cell membrane and the membrane permeability. In this study, we applied the Phe-modified dendrimers to a pH-sensitive drug delivery system into T cells. Dendrimers with different amino acids and acid anhydrides were synthesized, and their pH-responsive association with T cells and their subsets was investigated. The dendrimers modified with Phe and cyclohexanedicarboxylic acid (CHex) showed higher uptake into various cells, including Jurkat cells, CD3+ T cells, CD3 + CD4+ helper T cells and CD3 + CD8+ killer T cells. These dendrimers were internalized into T cells via endocytosis, and their cellular uptake was enhanced under weak acidic conditions (pH 6.5). Our results showed that Phe- and CHex-modified dendrimers have a delivery potential to T cells and their subsets, which may be useful for cancer immunotherapy.

Graphical abstract: Carboxy-terminal dendrimers with phenylalanine for a pH-sensitive delivery system into immune cells including T cells

Supplementary files

Article information

Article type
Paper
Submitted
09 Sept. 2021
Accepted
04 Dec. 2021
First published
07 Dec. 2021

J. Mater. Chem. B, 2022,10, 2463-2470

Carboxy-terminal dendrimers with phenylalanine for a pH-sensitive delivery system into immune cells including T cells

H. Shiba, M. Nishio, M. Sawada, M. Tamaki, M. Michigami, S. Nakai, I. Nakase, I. Fujii, A. Matsumoto and C. Kojima, J. Mater. Chem. B, 2022, 10, 2463 DOI: 10.1039/D1TB01980E

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