Discovery of Novel Multifunctional Molecules for Synergistic Theranostics Based on Vascular Normalization Targets

Area of Science:

• Oncology
• Drug Development
• Vascular Biology

Background:

• Tumor vascular abnormalities impede drug delivery and promote resistance.
• The vascular normalization theory explains paradoxical efficacy of antiangiogenic drugs combined with chemoradiotherapy.
• There is a need for innovative drugs targeting vascular normalization.

Purpose of the Study:

• To develop a novel twin drug combining vascular normalization and chemotherapy.
• To investigate the efficacy of a new vascular normalization-chemotherapy twin drug based on the QDAU5 molecule.
• To explore the potential of targeting EphrinB2 for synergistic cancer treatment.

Main Methods:

• Designed a twin drug based on the QDAU5 molecule, incorporating principles of twin drug design and controlled release.
• Evaluated the drug's membrane permeability, stability, and toxic payload release characteristics.
• Assessed the inhibitory activity of the twin drug against colorectal tumors in preclinical models.

Main Results:

• The QDAU5-based twin drug demonstrated favorable membrane permeability and stability.
• The drug exhibited rapid toxic payload release.
• Significant inhibitory activity against colorectal tumors was observed.

Conclusions:

• The developed vascular normalization-chemotherapy twin drug represents a novel therapeutic strategy.
• This finding enriches the vascular normalization theory and supports its application in new drug development.
• The QDAU5-based drug shows potential for overcoming colorectal tumor resistance.