Synergetic regulation of cancer cells and exhausted T cells to fight cold tumors with a fluorinated EGCG-based nanocomplex

Journal of Nanobiotechnology - Tập 21 - Trang 1-12 - 2023
Jinlin Zhang1,2, Mingyue Wang1,2, Doudou He1,2, Liang Zhang1,2, Tianqing Liu3, Kaikai Wang1,2
1Department of Pharmacy, Affiliated Cancer Hospital of Nantong University, Nantong University, Nantong, China
2School of Pharmacy, Nantong University, Nantong, China
3NICM Health Research Institute, Western Sydney University, Westmead, Australia

Tóm tắt

Immune therapy that targets PD-L1 (programmed cell death-ligand 1) is attractive to augment immune response by breaking the programmed cell death-1 (PD-1)/PD-L1 axis. However, T cell exhaustion associated with insufficient T cells infiltration may diminish the efficacy of cancer therapy. Here, we report a novel delivery system of FEGCG/FPEI@siTOX composed of fluorinated EGCG (FEGCG) and fluorinated polyethyleneimine (FPEI) for delivery of small interfering RNA anti-TOX (thymus high mobility group box protein, TOX) to treat tumor and metastasis. In this way, the reduction in PD-L1 expression by FEGCG can promote T-cell function, while inhibition of TOX expression with siTOX can alleviate T-cell exhaustion. FPEI are designed to deliver siRNA with high efficiency and low toxicity compared to classical PEI. Integrating FEGCG, FPEI and siTOX into such a novel system resulted in excellent anti-tumor and antimetastatic effects. It is a promising delivery system and potential strategy for the treatment of “cold” tumors.

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