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.