EGCG-enabled Deep Tumor Penetration of Phosphatase and Acidity Dual-responsive Nanotherapeutics for Combinatory...

Area of Science:

• Oncology
• Materials Science
• Nanotechnology

Background:

• Triple-negative breast cancer (TNBC) is characterized by dense collagen fibers that impede drug penetration and promote metastasis.
• Epigallocatechin-3-gallate (EGCG) shows potential in disrupting the tumor stroma.
• Developing effective drug delivery systems is crucial for TNBC treatment.

Purpose of the Study:

• To investigate the combined therapeutic effect of EGCG and a novel nanodrug for TNBC.
• To evaluate the role of EGCG in remodeling the tumor microenvironment and enhancing nanodrug efficacy.
• To assess the anti-tumor and anti-metastasis potential of the combination strategy.

Main Methods:

• EGCG was administered to disrupt the collagenous stroma by blocking the TGF-β/Smad pathway.
• A methotrexate (MTX)-loaded dual phosphate- and pH-responsive nanodrug (pHA@MOF-Au/MTX) was engineered.
• The nanodrug was surface-modified with a pH (low)-insertion peptide for enhanced cell binding.
• Sequential administration of EGCG and the nanodrug was performed in a TNBC mouse model.

Main Results:

• EGCG treatment remodeled the tumor stroma, enhancing nanodrug binding to tumor cells.
• High-concentration EGCG inhibited glutathione peroxidase, promoting tumor cell ferroptosis.
• The sequential treatment achieved a 79.9% tumor growth inhibition rate.
• A significant 96.8% reduction in pulmonary metastasis was observed.

Conclusions:

• The combination strategy of EGCG and pHA@MOF-Au/MTX demonstrates remarkable anti-tumor efficacy in TNBC.
• EGCG plays a key role in overcoming drug resistance by remodeling the tumor stroma and inducing ferroptosis.
• This study presents an innovative approach for improving chemo/chemodynamic therapy in TNBC.