Ovarian Tumor Targeting of Docetaxel-Loaded Liposomes Mediated by Luteinizing Hormone-Releasing Hormone Analogues
Ovarian Tumor Targeting of Docetaxel-Loaded Liposomes Mediated by Luteinizing Hormone-Releasing Hormone Analogues
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黄体化激素释放激素类似物介导的多西紫杉醇脂质体靶向卵巢肿瘤
DOI：
10.1055/s-0031-1296553
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发表时间：
2008-10
影响因子：
--
通讯作者：
Qin, Yao
中科院分区：
文献类型：
--
作者：
He, Qin;Zhang, Zhi-Rong;Song, Qing-Guo;Liu, Ji;Liu, Jie;Fu, Yao;Qin, Yao
摘要 最近的研究表明，黄体生成素释放激素（LHRH）类似物（LHRHa）与LHRH一样，能够特异性结合卵巢肿瘤细胞胞外膜上高表达的LHRH受体。作为靶向部分，LHRHa 可以介导多西紫杉醇脂质体的卵巢肿瘤靶向。在我们的研究中，采用合成的带负电荷的胆固醇琥珀酰亚胺（CHS）来制备带负电荷的多西紫杉醇脂质体，通过静电吸附将带正电荷的LHRHa与脂质体连接。建立了体内多西紫杉醇（CAS 114977-28-5，Doc）的HPLC测定法和卵巢癌异种移植模型，以研究多西紫杉醇、多西紫杉醇脂质体（Doc-Lipo）和LHRHa介导的多西紫杉醇脂质体（LHRHa-Doc-Lipo）在裸鼠体内的生物分布。 LHRHa-Doc-Lipo给药60分钟后，荷瘤裸鼠卵巢肿瘤中多西紫杉醇的浓度是Doc-Lipo的2.86倍，是Doc的9.02倍。与Doc-Lipo相比，LHRHa-Doc-Lipo使肝脏和脾脏中多西紫杉醇的浓度分别降低57%和34%。因此，LHRHa-Doc-Lipo表现出作为卵巢肿瘤化疗的主动靶向药物递送系统的潜力。
Abstract Recent studies indicate that luteinizing hormone-releasing hormone (LHRH) analogues (LHRHa), like LHRH, are able to specifically bind to LHRH receptors which are highly expressed on the extracellular membrane of ovarian tumor cells. As a targeting moiety, LHRHa can mediate the ovarian tumor targeting of docetaxel-loaded liposomes. In our study, synthesized negatively charged cholesterol succinimide (CHS) was employed for the preparation of negatively charged docetaxel-loaded liposomes, with which the positively charged LHRHa is linked via electrostatic absorption. An HPLC-based assay for determination of docetaxel (CAS 114977-28-5, Doc) in vivo and the model of ovarian cancer xenograft were established to investigat the biodistribution of docetaxel, docetaxel liposomes (Doc-Lipo), and LHRHa mediated docetaxel-loaded liposomes (LHRHa-Doc-Lipo) in nude mice. Sixty minutes after administration of LHRHa-Doc-Lipo, the concentration of docetaxel in the ovarian tumor was 2.86 times that of Doc-Lipo and 9.02 times that of Doc in the nude mice bearing ovarian tumor. LHRHa-Doc-Lipo decreased the concentration of docetaxel in the liver and spleen by 57% and 34%, respectively, as compared with Doc-Lipo. Therefore, LHRHa-Doc-Lipo exhibits potentiality as an active targeting drug delivery system for chemotherapy of ovarian tumor.
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DOI：
--
发表时间：
2003
期刊：
Foreign Medical Sciences Section of Maternal and Child Health
影响因子：
--
作者：
C. Ying
通讯作者：
C. Ying
影响因子：
9.8
作者：
P. Völker;C. Gründker;Oswald Schmidt;K. Schulz;G. Emons
通讯作者：
P. Völker;C. Gründker;Oswald Schmidt;K. Schulz;G. Emons
影响因子：
9.8
作者：
M. Miyazaki;A. Schally;A. Nagy;N. Lamharzi;G. Halmos;K. Szepesházi;P. Armatis
通讯作者：
M. Miyazaki;A. Schally;A. Nagy;N. Lamharzi;G. Halmos;K. Szepesházi;P. Armatis
影响因子：
10.8
作者：
Kocbek, Petra;Obermajer, Natasa;Kristl, Julijana
通讯作者：
Kristl, Julijana
影响因子：
10.8
作者：
Dharap, SS;Qiu, B;Minko, T
通讯作者：
Minko, T