Peng Yu, Li Zhe, Zhou Lei, Jian Qian, Yin Baoli, Sun Bo, Song Yinghui, Chen Hao, Tan Xianzheng, Duan Xiaohui, Liu Sulai, Peng Chuang, Song Guosheng
Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, China.
Hunan Engineering Research Center of Digital Hepatobiliary Medicine, Changsha, 410005, China.
J Nanobiotechnology. 2025 Aug 25;23(1):587. doi: 10.1186/s12951-025-03674-7.
Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide. Sonodynamic therapy (SDT) offers a non-invasive, deep-penetrating approach by using ultrasound to activate sonosensitizers and generate cytotoxic reactive oxygen species (ROS). Yet poor intratumoral delivery and low ROS quantum yields of existing agents have stalled clinical translation. Here, we present a synergistic SDT platform that overcomes these barriers by combining transient vasodilation of tumor microvessels with the clinically widely used Antianginal drug isosorbide mononitrate and an acceptor-donor-acceptor-donor-acceptor type organic nanosonosensitizer (BTz) engineered for a narrow bandgap and enhanced ultrasound responsiveness. Isosorbide mononitrate increases nanosonosensitizer accumulation by ~ 1.8-fold. Under ultrasound irradiation, nanosonosensitizer produced high ROS generation, resulting in 78% tumor growth inhibition in murine HCC models-nearly double that of SDT alone-without detectable systemic toxicity. Crucially, the near-infrared fluorescence of nanosonosensitizer enabled real-time, image-guided tracking of sonosensitizer uptake and therapeutic response. By repurposing a safe vasodilator and integrating it with a high-performance organic sonosensitizer, this work establishes a readily translatable, minimally invasive paradigm for precise SDT of localized, inoperable or metastatic HCC.
肝细胞癌（HCC）仍然是全球癌症死亡的主要原因。声动力疗法（SDT）通过利用超声波激活声敏剂并产生活性氧（ROS）来提供一种非侵入性、深部穿透性的方法。然而，现有药物的肿瘤内递送不佳和ROS量子产率低阻碍了临床转化。在此，我们提出了一种协同SDT平台，该平台通过将肿瘤微血管的短暂血管舒张与临床上广泛使用的抗心绞痛药物单硝酸异山梨酯以及为窄带隙和增强超声响应性而设计的受体-供体-受体-供体-受体型有机纳米声敏剂（BTz）相结合来克服这些障碍。单硝酸异山梨酯使纳米声敏剂的积累增加了约1.8倍。在超声照射下，纳米声敏剂产生了高ROS生成，在小鼠HCC模型中导致78%的肿瘤生长抑制——几乎是单独SDT的两倍——且没有可检测到的全身毒性。至关重要的是，纳米声敏剂的近红外荧光能够实时、图像引导跟踪声敏剂的摄取和治疗反应。通过重新利用一种安全的血管舒张剂并将其与高性能有机声敏剂整合，这项工作为局部、不可切除或转移性HCC的精确SDT建立了一种易于转化的微创模式。
