Anti-angiogenic nano-delivery system promotes tumor vascular normalizing and micro-environment reprogramming in solid...

Area of Science:

• Oncology
• Nanotechnology
• Biomedical Engineering

Background:

• Aberrant tumor vasculature creates a malignant tumor microenvironment (TME) that promotes tumor progression.
• Anti-angiogenic agents can temporarily normalize tumor vasculature, but prolonged normalization and its effects are understudied.

Purpose of the Study:

• To develop a nano-delivery system for sustained release of Vandetanib to achieve stable tumor vascular normalization.
• To investigate the impact of long-term vascular normalization on tumor perfusion, TME, and tumor progression in a breast cancer model.

Main Methods:

• Developed V@LDL NPs, a nano-delivery system for sustained release of Vandetanib (an anti-VEGFR2 inhibitor).
• Evaluated the stable tumor vascular normalizing effect in a 4T1 breast cancer model.
• Assessed improvements in tumor perfusion and reversal of TME abnormalities like hypoxia and heterogeneity.

Main Results:

• V@LDL NPs demonstrated a stable tumor vascular normalizing effect in the 4T1 breast cancer model.
• Long-term normalized vasculature led to improved tumor perfusion.
• Normalization reversed TME abnormalities and inhibited tumor progression.

Conclusions:

• Stable tumor vascular normalization is a viable strategy for long-term TME remodeling.
• Anti-angiogenic nano-delivery systems can achieve stable vascular normalization and offer therapeutic benefits in anti-cancer treatment.