Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and...

Area of Science:

• Oncology
• Immunology
• Nanomedicine

Background:

• Inflammation is a key driver of cancer growth and promotes thrombus formation, a major cause of cancer mortality.
• Tumor endothelial cells (TECs) exhibit inflamed phenotypes, contributing to both tumor progression and thrombosis.
• Epigallocatechin-3-O-gallate (EGCG), a green tea compound, has known anti-inflammatory properties, but its direct effect on TEC inflammation and anti-tumor activity was unclear.

Purpose of the Study:

• To investigate the anti-tumor effects of EGCG by targeting inflammation in TECs.
• To evaluate the efficacy of an EGCG-loaded cyclic RGD liposome delivery system (EGCG-MEND) in inhibiting tumor progression.

Main Methods:

• In vitro studies utilized quantitative PCR and immunofluorescence to assess EGCG's impact on TEC gene and protein expression.
• In vivo studies employed EGCG-MEND for targeted delivery to TECs in tumor-bearing mice.
• Analysis included inflammatory cytokine expression, NF-κB signaling, von Willebrand factor, and immune markers.

Main Results:

• EGCG significantly reduced inflammatory cytokine expression (TNF-α, IL-6, IL-8, IL-1β) in TECs via NF-κB inhibition.
• EGCG-MEND effectively inhibited TEC inflammation and thrombus formation within tumors.
• EGCG-MEND enhanced anti-tumor immunity by decreasing PD-L1 expression and promoting CD8+ T cell infiltration.

Conclusions:

• EGCG-MEND demonstrates significant anti-tumor potential by normalizing the tumor immune microenvironment.
• Targeting TEC inflammation with EGCG-MEND effectively inhibits thrombosis.
• This approach offers a novel strategy for cancer therapy by modulating the tumor microenvironment.