YAP/TAZ Inhibitor-Based Drug Delivery System for Selective Tumor Accumulation and Cancer Combination Therapy

Area of Science:

• Oncology
• Materials Science
• Nanotechnology

Background:

• Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key drivers in cancer development and therapy resistance.
• Pharmacological inhibition of YAP/TAZ is a promising strategy for cancer treatment.
• Niflumic acid (NA), a YAP/TAZ inhibitor, has limited clinical utility due to poor in vivo half-life.

Purpose of the Study:

• To develop improved prodrug strategies for YAP/TAZ inhibition.
• To create self-assembled nanoparticles for enhanced delivery of niflumic acid.
• To investigate a nanocombination therapy for breast cancer treatment.

Main Methods:

• Synthesized a series of niflumic acid-based prodrug polymers.
• Investigated physicochemical properties of self-assembled nanoparticles.
• Utilized optimal prodrug polymer as a micellar nanocarrier for receptor tyrosine kinase inhibitors (RTKIs).

Main Results:

• Developed prodrug polymers that self-assemble into nanoparticles, improving niflumic acid bioavailability.
• The optimal prodrug nanocarrier selectively accumulated in tumors.
• Combination therapy with RTKIs (e.g., Dasatinib) synergistically inhibited tumor growth.

Conclusions:

• Prodrug polymer nanoparticles offer a viable strategy to overcome niflumic acid's limitations.
• Nanocombination therapy demonstrates enhanced efficacy in preclinical breast cancer models.
• This approach holds potential for improved cancer treatment strategies.