T cells, also known as lymphocytes, have important roles in various immune reactions. However, there are only a few reports on delivery systems into T cells.
The T cell association of these dendrimers was examined at different pH and temperatures using fluorescence-activated cell sorting, where murine splenocytes stained with an anti-CD3 antibody were used. Along with this, the association of PAMAM-CHex-Phe and PAMAM-Phe-CHex with some culture cell lines and T cell subsets, such as CD4-positive helper T cells (CD3+CD4+), CD8- positive killer T cells (CD3+CD8+) and activated T cells (CD3+CD69+) was also examined. In order to confirm the internalization of these dendrimers into T cells, Assoc. Prof. Kojima and her co-workers used confocal microscopic imaging to observe the intracellular distribution of PAMAM-CHex-Phe and PAMAM-Phe-CHex.
Assoc. Prof. Kojima says that “although T cells play important roles in various immune reactions, there are only a few reports on delivery systems into T cells. 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.”
This experimental study by Assoc. Prof. Kojima and her co-workers has successfully presented the findings in terms of a) Synthesis and pH sensitivity of the carboxy-terminal dendrimers bearing Phe; b) pH-responsive association of the carboxy-terminal dendrimers bearing Phe with T cells and T cell subsets including activated T cells; c) Internalization of PAMAM-Phe-CHex and PAMAM-CHex-Phe into T cells.
She concludes that their “results showed that Phe- and CHex-modified dendrimers have a delivery potential to T cells and their subsets. This will play a key role in cancer immunotherapy.”
Activation of lymph node-resident helper T cells and killer T cells as well as suppression of regulatory T cells localized in tumor tissues is necessary in cancer immunotherapy. Hence, based on the pH-responsive properties, the findings (dendrimers) obtained by Assoc. Prof. Kojima and her co-workers are important for the development of nanoplatforms for direct delivery to T cells to control the functions of T cells, which are useful for cancer immunotherapy.
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