Synergetic regulation of cancer cells and exhausted T cells to fight cold tumors with a fluorinated EGCG-based nanocomplex
-
Published:2023-11-14
Issue:1
Volume:21
Page:
-
ISSN:1477-3155
-
Container-title:Journal of Nanobiotechnology
-
language:en
-
Short-container-title:J Nanobiotechnol
Author:
Zhang Jinlin,Wang Mingyue,He Doudou,Zhang Liang,Liu Tianqing,Wang Kaikai
Abstract
AbstractImmune 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.
Funder
National Health and Medical Research Council National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
Reference41 articles.
1. Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2022;22(2):85–96. 2. Chowell D, Yoo SK, Valero C, Pastore A, Krishna C, Lee M, Hoen D, Shi H, Kelly DW, Patel N, Makarov V, Ma X, Vuong L, Sabio EY, Weiss K, Kuo F, Lenz TL, Samstein RM, Riaz N, Adusumilli PS, Balachandran VP, Plitas G, Ari Hakimi A, Abdel-Wahab O, Shoushtari AN, Postow MA, Motzer RJ, Ladanyi M, Zehir A, Berger MF, Gonen M, Morris LGT, Weinhold N, Chan T. A., Improved prediction of immune checkpoint blockade efficacy across multiple cancer types. Nat Biotechnol. 2022;40(4):499–506. 3. Kubli SP, Berger T, Araujo DV, Siu LL, Mak TW. Beyond immune checkpoint blockade: emerging immunological strategies. Nat Rev Drug Discov. 2021;20(12):899–919. 4. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5. 5. Han HS, Jeong S, Kim H, Kim HD, Kim AR, Kwon M, Park SH, Woo CG, Kim HK, Lee KH, Seo SP, Kang HW, Kim WT, Kim WJ, Yun SJ, Shin EC. TOX-expressing terminally exhausted tumor-infiltrating CD8(+) T cells are reinvigorated by co-blockade of PD-1 and TIGIT in Bladder cancer. Cancer Lett. 2021;499:137–47.
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|