Vicious-cycle-breaking antiangiogenic nano-delivery systems potentiate and simplify the tumor vascular normalization...

Area of Science:

• Oncology
• Nanomedicine
• Immunotherapy

Background:

• Tumor vascular normalization strategies face challenges in drug dosage and timing.
• Tumor-associated macrophages (TAMs) can interfere with anti-angiogenesis therapy.
• Current methods require precise monitoring of transient normalization windows.

Purpose of the Study:

• To develop and compare two anlotinib (ANB) delivery systems: sialic acid-cholesterol conjugate-modified liposomes (ANB-SL) and polysialic acid-modified electrostatic complexes (ANB-PSA).
• To evaluate the efficacy of ANB-SL in achieving tumor vascular normalization and enhancing anti-tumor effects.
• To overcome clinical bottlenecks in vascular normalization therapy.

Main Methods:

• Preparation and comparison of ANB-SL and ANB-PSA drug delivery systems.
• Assessment of ANB-SL targeting of TAMs and tumor enrichment.
• Evaluation of ANB-SL's impact on tumor vasculature, immune cell infiltration, and tumor cell proliferation.

Main Results:

• ANB-SL specifically targets TAMs, leading to their elimination and inhibition of vascular endothelial cells, achieving tumor vascular normalization.
• ANB-SL promotes CD8+ T cell infiltration and shifts the tumor microenvironment (TME) towards an immune-activated state.
• ANB-SL enhances drug delivery efficiency and exerts anti-tumor cytotoxic effects post-vascular normalization, independent of precise timing.

Conclusions:

• ANB-SL effectively normalizes tumor vasculature and enhances anti-tumor immunity by targeting TAMs.
• This novel delivery system simplifies tumor vascular normalization strategies, offering a potent approach for cancer treatment.
• ANB-SL provides new therapeutic insights by integrating vascular normalization with direct anti-tumor effects.