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Lipid Nanoparticle Delivery System for Normalization of Tumor Microenvironment and Tumor Vascular Structure
Heejin Ha1, Yonghyun Choi1,2, Na-Hyeon Kim3
1School of Integrative Engineering, Chung-Ang University, Seoul 06974, Republic of Korea.
Biomaterials Research
|February 12, 2025
Summary
This study introduces a novel pH-sensitive liposome system (OD_PSL@AKB) that delivers oxygen and razuprotafib to tumors. It effectively combats tumor hypoxia and abnormal vasculature, enhancing treatment efficacy.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Drug Delivery Systems
Background:
- Tumor growth relies on angiogenesis, leading to abnormal vasculature.
- Tumor microenvironment (TME) hypoxia exacerbates pro-angiogenic factor secretion (e.g., VEGF).
- Hypoxic TME compromises radiotherapy, immunotherapy, and chemotherapy efficacy.
Purpose of the Study:
- To develop a pH-sensitive liposome (PSL) system for co-delivering oxygen (OD) and razuprotafib (AKB-9778).
- To investigate the system's ability to alleviate tumor hypoxia and normalize vasculature.
- To assess the impact on therapeutic efficacy.
Main Methods:
- Development of a pH-sensitive liposome (PSL) system, OD_PSL@AKB.
- Co-delivery of oxygen (OD) and razuprotafib (AKB-9778) to tumors.
- Evaluation in hypoxic endothelial cell/cancer cell cocultures.
Main Results:
- The OD_PSL@AKB system rapidly responds to acidic TME.
- Alleviates hypoxia and inhibits vascular endothelial growth factor (VEGF) secretion.
- Restores VE-cadherin expression and normalizes tumor vasculature.
Conclusions:
- OD_PSL@AKB demonstrates potential for normalizing tumor vasculature.
- This approach may improve the efficacy of cancer therapies.
- Targeting TME hypoxia is a promising strategy for cancer treatment.
