Pharmaceutics (Mar 2023)

T Cell-Association of Carboxy-Terminal Dendrimers with Different Bound Numbers of Phenylalanine and Their Application to Drug Delivery

  • Hiroya Shiba,
  • Tomoka Hirose,
  • Yunshen Fu,
  • Masataka Michigami,
  • Ikuo Fujii,
  • Ikuhiko Nakase,
  • Akikazu Matsumoto,
  • Chie Kojima

DOI
https://doi.org/10.3390/pharmaceutics15030888
Journal volume & issue
Vol. 15, no. 3
p. 888

Abstract

Read online

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.

Keywords