Quaternary ammonium salt microspheres loaded with vascular disrupting agents for targeted interventional therapy of hepatocellular carcinoma

作者：Xin Su, Enqi Qiao, Gao‐Jun Teng, Fei Xiong · 发表于：Acta Biomaterialia · 年份：2025 · DOI：10.1016/j.actbio.2025.07.055 · 被引用次数：5 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Multiple Myeloma Research and Treatments、Cancer, Hypoxia, and Metabolism

Hepatocellular carcinoma (HCC) is a severe health condition that poses a significant threat to life, characterized by high incidence and mortality rates. Transarterial chemoembolization (TACE) is the primary treatment modality for intermediate and advanced stages of HCC. TACE often fails to completely block all tumor blood supplies, and the hypoxic environment following embolization can lead to neoangiogenesis, negatively impacting the therapeutic efficacy and prognosis of TACE. Combretastatin A4 phosphate (CA4P), as a vascular disrupting agent (VDA), can destroy the tumor's vascular network, inhibit the formation of new blood vessels, and induce ischemic necrosis of the tumor, potentially addressing this issue. Currently, there are no clinically available positively charged microspheres capable of loading CA4P. Based on this, quaternary ammonium salt-based drug-eluting microspheres have been designed to load and sustain the release of CA4P. In vitro and in vivo experiments have demonstrated that CA4P-loaded microsphere therapy can further damage the tumor's vascular system, exacerbate tumor necrosis, and significantly reduce the expression of CD31 and VEGF. This method effectively addresses the current clinical challenge of incomplete tumor blood supply blockage in TACE and the issues of neoangiogenesis caused by the hypoxic environment post-embolization, potentially improving the therapeutic efficacy and prognosis of TACE. STATEMENT OF SIGNIFICANCE: Hepatocellular carcinoma...