研究动态
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使用基于氟化 EGCG 的纳米复合物协同调节癌细胞和耗尽的 T 细胞来对抗冷肿瘤。

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

发表日期:2023 Nov 14
作者: Jinlin Zhang, Mingyue Wang, Doudou He, Liang Zhang, Tianqing Liu, Kaikai Wang
来源: JOURNAL OF NANOBIOTECHNOLOGY

摘要:

针对 PD-L1(程序性细胞死亡配体 1)的免疫疗法通过破坏程序性细胞死亡 1 (PD-1)/PD-L1 轴来增强免疫反应,具有吸引力。然而,与 T 细胞浸润不足相关的 T 细胞耗竭可能会降低癌症治疗的功效。在这里,我们报道了一种由氟化EGCG(FEGCG)和氟化聚乙烯亚胺(FPEI)组成的新型FEGCG/FPEI@siTOX递送系统,用于递送小干扰RNA抗TOX(胸腺高迁移率族盒蛋白,TOX)来治疗肿瘤和转移。这样,FEGCG减少PD-L1表达可以促进T细胞功能,而siTOX抑制TOX表达可以缓解T细胞耗竭。与经典 PEI 相比,FPEI 旨在以高效率和低毒性递送 siRNA。将 FEGCG、FPEI 和 siTOX 集成到这样一个新颖的系统中,产生了优异的抗肿瘤和抗转移效果。这是一种很有前景的输送系统,也是治疗“冷”肿瘤的潜在策略。© 2023。作者。
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.© 2023. The Author(s).