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<p>Tirapazamine (TPZ) is a bioreductive agent with selective antitumor activity under hypoxic conditions; however, its systemic toxicity and delivery efficiency limit its clinical application. This study aimed to develop a TPZ delivery system based on nanobubbles (NBs), combining ultrasound-targeted microbubble destruction (UTMD) and transcatheter arterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) to enhance therapeutic efficacy and reduce adverse effects. TPZ-NBs were fabricated using a high-shear dispersion method and characterized for their physicochemical properties, encapsulation efficiency, and drug release profiles. In vitro studies evaluated the effects of TPZ-NBs on hepatoma cell proliferation and migration under hypoxic conditions. Using a rabbit VX2 liver cancer model, we compared the control group, TACE group, TPZ-NBs + TACE group, and TPZ-NBs + UTMD + TACE group in terms of tumor necrosis, drug delivery efficiency, and safety profiles. TPZ-NBs demonstrated favorable encapsulation efficiency (35.81%) and sustained-release characteristics (58% cumulative release over 48&#xa0;h). In vitro experiments showed that TPZ-NBs significantly inhibited hepatoma cell proliferation and migration under hypoxic conditions. In animal studies, the TPZ-NBs + UTMD + TACE group significantly enhanced intratumoral drug delivery efficiency, induced tumor cell apoptosis, reduced microvessel density (MVD), and decreased tumor recurrence. Compared to other groups, this combination therapy exhibited higher tumor necrosis rates and deeper drug penetration while maintaining favorable safety profiles. The combination of TPZ-NBs with UTMD and TACE represents an efficient and safe therapeutic strategy that overcomes the limitations of conventional TACE, offering new possibilities for hepatocellular carcinoma treatment.</p>

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Experimental study on combined treatment of hepatocellular carcinoma using tirapazamine-loaded nanobubbles and transcatheter arterial embolization

  • 期刊论文

  • 发表日期：

    2026年3月9日

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  • Yifan Li,
  • Zhen Li,
  • Yuyuan Zhang,
  • Menghe Wang,
  • Shuwen Ye,
  • Bailu Wu,
  • Peijie Lv,
  • Pengfei Pang,
  • Xin Li,
  • Pengchao Zhan

摘要

Tirapazamine (TPZ) is a bioreductive agent with selective antitumor activity under hypoxic conditions; however, its systemic toxicity and delivery efficiency limit its clinical application. This study aimed to develop a TPZ delivery system based on nanobubbles (NBs), combining ultrasound-targeted microbubble destruction (UTMD) and transcatheter arterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) to enhance therapeutic efficacy and reduce adverse effects. TPZ-NBs were fabricated using a high-shear dispersion method and characterized for their physicochemical properties, encapsulation efficiency, and drug release profiles. In vitro studies evaluated the effects of TPZ-NBs on hepatoma cell proliferation and migration under hypoxic conditions. Using a rabbit VX2 liver cancer model, we compared the control group, TACE group, TPZ-NBs + TACE group, and TPZ-NBs + UTMD + TACE group in terms of tumor necrosis, drug delivery efficiency, and safety profiles. TPZ-NBs demonstrated favorable encapsulation efficiency (35.81%) and sustained-release characteristics (58% cumulative release over 48 h). In vitro experiments showed that TPZ-NBs significantly inhibited hepatoma cell proliferation and migration under hypoxic conditions. In animal studies, the TPZ-NBs + UTMD + TACE group significantly enhanced intratumoral drug delivery efficiency, induced tumor cell apoptosis, reduced microvessel density (MVD), and decreased tumor recurrence. Compared to other groups, this combination therapy exhibited higher tumor necrosis rates and deeper drug penetration while maintaining favorable safety profiles. The combination of TPZ-NBs with UTMD and TACE represents an efficient and safe therapeutic strategy that overcomes the limitations of conventional TACE, offering new possibilities for hepatocellular carcinoma treatment.