Development of in Situ Forming Thermosensitive Hydrogel for Radiotherapy Combined with Chemotherapy in a Mouse Model of Hepatocellular Carcinoma

被引:46
|
作者
Peng, Cheng-Liang [1 ,2 ,3 ]
Shih, Ying-Hsia [1 ,2 ,3 ]
Liang, Kuo-Sheng [1 ,2 ]
Chiang, Ping-Fang [3 ]
Yeh, Chung-Hsin [3 ]
Tang, I-Chang [3 ]
Yao, Cheng-Jung [1 ,2 ]
Lee, Shin-Yi [1 ,2 ]
Luo, Tsai-Yueh [3 ]
Shieh, Ming-Jium [1 ,2 ,4 ,5 ]
机构
[1] Natl Taiwan Univ, Inst Biomed Engn, Coll Med, Taipei 100, Taiwan
[2] Natl Taiwan Univ, Coll Engn, Taipei 100, Taiwan
[3] Inst Nucl Energy Res, Isotope Applicat Div, Tao Yuan 325, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan
[5] Coll Med, Taipei, Taiwan
关键词
thermally responsive material; chemotherapy; radiotherapy; drug delivery; hepatocellular carcinoma; CANCER; LIVER; BRACHYTHERAPY; METASTASES; INJECTION; MICELLES; HEPATOMA; DELIVERY; THERAPY; SURGERY;
D O I
10.1021/mp3006424
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
This study evaluated a system for local cancer radiotherapy combined with chemotherapy. The delivery system is a thermosensitive hydrogel containing a therapeutic radionuclide (Re-188-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/Re-188-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 Re-188-Tin loaded hydrogel than for Na Re-188 perrhenate (Na (ReO4)-Re-188). The hydrogel after thermal transition kept the radionuclide inside the tumor, whereas free Re-188 perrhenate ((ReO4)-Re-188) diffused quickly from the tumor. The tumor growth was more profoundly inhibited by treatment with Lipo-Dox/Re-188-Tin hydrogel (with up to 80% regression of well-established tumors on day 32) than treatment with either Re-188-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.
引用
收藏
页码:1854 / 1864
页数:11
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