Microfluidics-enabled fluorinated assembly of EGCG-ligands-siTOX nanoparticles for synergetic tumor cells and exhausted t cells regulation in cancer immunotherapy.
J Nanobiotechnology
; 22(1): 90, 2024 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-38439048
ABSTRACT
Immune checkpoint inhibitor (ICI)-derived evolution offers a versatile means of developing novel immunotherapies that targets programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) axis. However, one major challenge is T cell exhaustion, which contributes to low response rates in "cold" tumors. Herein, we introduce a fluorinated assembly system of LFNPs/siTOX complexes consisting of fluorinated EGCG (FEGCG), fluorinated aminolauric acid (LA), and fluorinated polyethylene glycol (PEG) to efficiently deliver small interfering RNA anti-TOX (thymus high mobility group box protein, TOX) for synergistic tumor cells and exhausted T cells regulation. Using a microfluidic approach, a library of LFNPs/siTOX complexes were prepared by altering the placement of the hydrophobe (LA), the surface PEGylation density, and the siTOX ratio. Among the different formulations tested, the lead formulation, LFNPs3-3/siTOX complexes, demonstrated enhanced siRNA complexation, sensitive drug release, improved stability and delivery efficacy, and acceptable biosafety. Upon administration by the intravenous injection, this formulation was able to evoke a robust immune response by inhibiting PD-L1 expression and mitigating T cell exhaustion. Overall, this study provides valuable insights into the fluorinated assembly and concomitant optimization of the EGCG-based delivery system. Furthermore, it offers a promising strategy for cancer immunotherapy, highlighting its potential in improving response rates in ''cold'' tumors.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Neoplasias
Idioma:
En
Revista:
J Nanobiotechnology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China