Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
Mol Pharm. 2013 May 6;10(5):1854-64. doi: 10.1021/mp3006424. Epub 2013 Apr 1.
This study evaluated a system for local cancer radiotherapy combined with chemotherapy. The delivery system is a thermosensitive hydrogel containing a therapeutic radionuclide ((188)Re-Tin colloid) and a chemotherapeutic drug (liposomal doxorubicin). The thermosensitive PCL-PEG-PCL copolymer was designed to spontaneously undergo a sol-gel phase transition in response to temperature, remaining liquid at room temperature and rapidly forming a gel at body temperature. A scanning electron microscope was used to observe the microstructure of the fully loaded hydrogel. Release of radionuclide and doxorubicin from the hydrogel was slow, and the system tended to remain stable for at least 10 days. After the intratumoral administration of Lipo-Dox/(188)Re-Tin hydrogel in mice with hepatocellular carcinoma (HCC), its retention by the tumor, spatiotemporal distribution, and therapeutic effect were evaluated. The residence time in the tumor was significantly longer for (188)Re-Tin loaded hydrogel than for Na (188)Re perrhenate (Na (188)ReO4). The hydrogel after thermal transition kept the radionuclide inside the tumor, whereas free (188)Re perrhenate ((188)ReO4) diffused quickly from the tumor. The tumor growth was more profoundly inhibited by treatment with Lipo-Dox/(188)Re-Tin hydrogel (with up to 80% regression of well-established tumors on day 32) than treatment with either (188)Re-Tin hydrogel or Lipo-Dox hydrogel. Therefore, this injectable and biodegradable hydrogel may offer the advantage of focusing radiotherapy and chemotherapy locally to maximize their effects on hepatocellular carcinoma.
本研究评估了一种局部癌症放射治疗与化疗相结合的系统。该输送系统是一种热敏水凝胶，含有治疗性放射性核素（(188)Re-锡胶体）和化疗药物（脂质体阿霉素）。热敏 PCL-PEG-PCL 共聚物的设计目的是在温度响应下自发经历溶胶-凝胶相转变，在室温下保持液态，并在体温下迅速形成凝胶。扫描电子显微镜用于观察完全负载水凝胶的微观结构。放射性核素和阿霉素从水凝胶中的释放缓慢，该系统至少在 10 天内趋于保持稳定。在荷肝癌（HCC）小鼠中经皮瘤内给予脂质体阿霉素/（188）Re-锡水凝胶后，评估其在肿瘤中的保留、时空分布和治疗效果。负载（188）Re-锡的水凝胶在肿瘤中的停留时间明显长于 Na（188）Re 高锝酸盐（Na（188）ReO4）。热转变后的水凝胶将放射性核素保持在肿瘤内，而游离（188）Re 高锝酸盐（(188)ReO4）则从肿瘤中迅速扩散。与单独使用（188）Re-锡水凝胶或脂质体阿霉素水凝胶相比，用脂质体阿霉素/（188）Re-锡水凝胶治疗更能显著抑制肿瘤生长（第 32 天，已建立的肿瘤有高达 80%的消退）。因此，这种可注射和可生物降解的水凝胶可能具有局部聚焦放射治疗和化疗的优势，以最大限度地提高其对肝癌的疗效。
