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

Jinlin Zhang; Mingyue Wang; Doudou He; Liang Zhang; Tianqing Liu; Kaikai Wang

doi:10.1186/s12951-023-02205-6

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

Jinlin Zhang, Mingyue Wang, Doudou He, Liang Zhang, Tianqing Liu, Kaikai Wang

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

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.

Original language	English
Article number	420
Number of pages	12
Journal	Journal of Nanobiotechnology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12951-023-02205-6
Publication status	Published - Dec 2023

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© 2023, The Author(s).

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Cite this

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

abstract = "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.",

author = "Jinlin Zhang and Mingyue Wang and Doudou He and Liang Zhang and Tianqing Liu and Kaikai Wang",

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doi = "10.1186/s12951-023-02205-6",

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AU - Zhang, Jinlin

AU - Wang, Mingyue

AU - He, Doudou

AU - Zhang, Liang

AU - Liu, Tianqing

AU - Wang, Kaikai

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - https://hdl.handle.net/1959.7/uws:75034

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DO - 10.1186/s12951-023-02205-6

M3 - Article

C2 - 37957632

SN - 1477-3155

VL - 21

JO - Journal of Nanobiotechnology

JF - Journal of Nanobiotechnology

IS - 1

M1 - 420

ER -

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

Abstract

Bibliographical note

Open Access - Access Right Statement

UN SDGs

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