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

Area of Science:

• Nanomedicine
• Immunology
• Drug Delivery

Background:

• T cells in lymph nodes are crucial for cancer immunotherapy.
• Dendrigraft polylysines (DGLs) are effective nanoplatforms in nanomedicine.
• Targeting T cells for drug delivery remains a challenge.

Purpose of the Study:

• To develop and characterize DGL-CHex-Phe polymers for T cell drug delivery.
• To evaluate the drug loading and release capabilities of these polymers.
• To assess the in vivo efficacy of the DGL-CHex-Phe nanoplatform in targeting lymph node T cells.

Main Methods:

• Synthesis of DGL-CHex-Phe polymers using varying DGL generations and Phe ratios.
• Assessment of polymer association and internalization by Jurkat T cells.
• Loading of hydrophobic paclitaxel (PTX) onto selected polymers.
• Evaluation of PTX-loaded polymer cytotoxicity against Jurkat cells.
• Intradermal injection in vivo to determine lymph node accumulation and T cell co-localization.

Main Results:

• Higher generation DGL-CHex-Phe polymers showed enhanced association and internalization by T cells.
• DGL(G3)-CHex-Phe93 demonstrated superior paclitaxel loading and retention.
• PTX-loaded DGL(G3)-CHex-Phe93 exhibited comparable cytotoxicity to free PTX.
• Intradermal injection led to efficient accumulation of DGL(G3)-CHex-Phe93 in lymph nodes, with partial co-localization with T cells.

Conclusions:

• DGL(G3)-CHex-Phe93 is a promising nanoplatform for delivering hydrophobic drugs to T cells.
• This nanoplatform facilitates drug delivery into immune cells within lymph nodes.
• The findings support the potential of DGL-CHex-Phe for cancer immunotherapy applications.