Citation: Cheng-Zhe Gao, Hao-Ran Jia, Tian-Yu Wang, Xiao-Yu Zhu, Xiaofeng Han, Fu-Gen Wu. A dual drug-loaded tumor vasculature-targeting liposome for tumor vasculature disruption and hypoxia-enhanced chemotherapy[J]. Chinese Chemical Letters, ;2025, 36(1): 109840. doi: 10.1016/j.cclet.2024.109840 shu

A dual drug-loaded tumor vasculature-targeting liposome for tumor vasculature disruption and hypoxia-enhanced chemotherapy

State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China

wufg@seu.edu.cn

Received Date: 24 January 2024
Revised Date: 25 March 2024
Accepted Date: 27 March 2024
Available Online: 28 March 2024

Figures(5)

Vascular disrupting agents (VDAs) can destroy tumor vasculature and lead to tumor ischemia and hypoxia, resulting in tumor necrosis. However, VDAs are easy to induce the upregulation of genes that are associated with cancer cell drug resistance and angiogenesis in tumor cells. Hypoxia-activated chemotherapy will be an ideal supplement to VDAs therapy since it can help to fully utilize the ischemia and hypoxia induced by VDAs to realize a synergistic antitumor therapeutic outcome. Here, we design a liposome whose surface is modified with a tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA, which can specifically target tumor vessels and stroma) and whose aqueous cavity and lipid bilayer are loaded by a hypoxia-activatable drug banoxantrone dihydrochloride (AQ4N) and a VDA combretastatin A4 (CA4), respectively. CA4 can selectively target vascular endothelial cells and destroy the tumor blood vessels, which will cause the rapid inhibition of blood flow in tumor and enhance the hypoxia in the tumor region. As a consequence, AQ4N can exert its boosted cytotoxicity under the enhanced hypoxic environment. The as-prepared liposome with a uniform particle size exhibits good stability and high cancer cell killing efficacy in vitro. In addition, in vivo experiments confirm the excellent tumor-targeting/accumulation, tumor vasculature-damaging, and tumor inhibition effects of the liposome. This work develops a liposomal which can achieve safe and effective tumor suppression without external stimulus excitation by only single injection, and is expected to benefit the future development of effective antitumor liposomal drugs.
- Tumor-homing peptide,
- Liposome,
- Vascular disrupting agents,
- Chemotherapy,
- Hypoxia-activated
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