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

• Published in: Journal of nanobiotechnology Vol. 21; no. 1; pp. 1 - 420
• Main Authors: Zhang, Jinlin, Wang, Mingyue, He, Doudou, Zhang, Liang, Liu, Tianqing, Wang, Kaikai
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 14-11-2023; BioMed Central; BMC
• Subjects: Anticancer properties; Apoptosis; Cancer; Cancer therapies; Care and treatment; Catechin; Cell cycle; Cell death; Chemical properties; Cold treatment; Cytotoxicity; Delivery system; Drug delivery systems; Drug therapy; Drugs; Efficiency; EGCG; Epigallocatechin gallate; Fatigue; Fluorination; Fluorine; Fluorine compounds; Health aspects; High mobility group proteins; Hydrogen; Immune response; Immune system; Immunotherapy; Lymphocytes; Lymphocytes T; Metastases; Metastasis; Nanoparticles; PD-1 protein; PD-L1 protein; Pharmaceutical research; Polyethyleneimine; Polyphenols; Programmed death-ligand 1; Proteins; siRNA; T cells; Technology application; Toxicity; Tumor necrosis factor-TNF; Tumors; Vehicles; China
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-02205-6

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.