Chen Siyu, Sun Yiyang, Xie Yangla, Liu Yanpeng, Hu Haitao, Xie Chang, Xu Shengjun, Zhang Zhouxing, Zhang Jing, Shen Youqing, Xu Xiao, Qiu Nasha
The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, Hangzhou 310053, China.
Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, China.
ACS Appl Mater Interfaces. 2025 Jan 15;17(2):2899-2910. doi: 10.1021/acsami.4c13433. Epub 2024 Oct 25.
Hepatocellular carcinoma (HCC) is a highly malignant tumor that is resistant to chemotherapy and immunotherapy. Icaritin (ICT), a traditional Chinese medicine, has been reported as an immunoregulatory agent for treating advanced unresectable HCC. ICT induces mitophagy to cause immunogenic cell death (ICD); however, the poor bioavailability of ICT limits its therapeutic efficacy and clinical use. Therefore, this study aimed to assess the effect of using the poly(2-(-oxide-,-diethylamino) ethyl methacrylate)--poly(ε-caprolactone) copolymer (OPDEA-PCL) to encapsulate ICT into nanoparticles (ICT NPs). OPDEA-PCL/ICT NPs colocalized with the mitochondria, promoting the ICD induction effect of ICT in mouse HCC H22 cells. In the H22 subcutaneous tumor model, intravenously injected OPDEA-PCL/ICT NPs quickly accumulated in the tumor and efficiently activated systemic anticancer immunogenicity through their effects on mitophagy. The resulting tumor suppression rate was 60%, which was significantly higher than that of free ICT and poly(ethylene glycol) (PEG)-PCL/ICT NPs. Furthermore, mouse survival was also prolonged by nearly 2-fold with OPDEA-PCL/ICT NPs compared with PBS. In summary, this approach provides valuable insights into improving the immunotherapeutic efficacy of ICT for HCC.
肝细胞癌（HCC）是一种对化疗和免疫疗法具有抗性的高度恶性肿瘤。淫羊藿素（ICT）是一种中药，已被报道为治疗晚期不可切除HCC的免疫调节剂。ICT诱导线粒体自噬以引发免疫原性细胞死亡（ICD）；然而，ICT较差的生物利用度限制了其治疗效果和临床应用。因此，本研究旨在评估使用聚（2-（-氧代-，-二乙氨基）乙基甲基丙烯酸酯）-聚（ε-己内酯）共聚物（OPDEA-PCL）将ICT封装成纳米颗粒（ICT NPs）的效果。OPDEA-PCL/ICT NPs与线粒体共定位，促进了ICT在小鼠HCC H22细胞中的ICD诱导作用。在H22皮下肿瘤模型中，静脉注射的OPDEA-PCL/ICT NPs迅速在肿瘤中积累，并通过其对线粒体自噬的作用有效激活全身抗癌免疫原性。由此产生的肿瘤抑制率为60%，显著高于游离ICT和聚乙二醇（PEG）-PCL/ICT NPs。此外，与PBS相比，OPDEA-PCL/ICT NPs使小鼠生存期延长了近2倍。总之，该方法为提高ICT对HCC的免疫治疗效果提供了有价值的见解。
