Hydrophobic Drug Delivery into T Cells Using Carboxy‐Terminal Phenylalanine‐Modified Dendrigraft Polylysines

ABSTRACT T cells in the lymph nodes play an important role in cancer immunotherapy. Dendrigraft polylysines (DGLs) are potent nanoplatforms used in nanomedicine. In the present study, DGLs were modified with 1,2‐cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe) to produce DGL‐CHex‐Phe for drug delivery into T cells. Various DGL‐CHex‐Phe polymers were synthesized using different generations of DGL by reacting with Phe at different ratios. DGL‐CHex‐Phe polymers with a higher generation and more Phe efficiently associated with Jurkat cells, a T cell model. These polymers are internalized by T cells via an amino acid transporter and/or direct membrane association. The hydrophobic model drug, paclitaxel (PTX), was loaded onto the polymers. DGL(G3)‐CHex‐Phe93 loaded the most PTX molecules among them, and most of them were retained therein for 3 h. PTX‐loaded polymers exhibited cytotoxic effects against Jurkat cells at a level similar to that of free PTX. DGL(G3)‐CHex‐Phe93 efficiently accumulated in lymph nodes after intradermal injection, which was partially co‐localized with T cells. These results suggested that DGL(G3)‐CHex‐Phe93 is useful for the delivery of hydrophobic drugs into immune cells including T cells in lymph nodes.