载脂蛋白米托蒽醌脂质体修饰的黄体生成素释放激素受体特异性肽的药代动力学、分布和抗肿瘤疗效。
Pharmacokinetics, distribution and anti-tumor efficacy of liposomal mitoxantrone modified with a luteinizing hormone-releasing hormone receptor-specific peptide.
机构信息
Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Pharmaceutical College, Hebei University of Chinese Medicine, Shijiazhuang City, Hebei Province, China.
出版信息
Int J Nanomedicine. 2018 Feb 26;13:1097-1105. doi: 10.2147/IJN.S150512. eCollection 2018.
BACKGROUND
A previous study developed a novel luteinizing hormone-releasing hormone (LHRH) receptor-targeted liposome. The aim of this study was to further assess the pharmacokinetics, biodistribution, and anti-tumor efficacy of LHRH receptor-targeted liposomes loaded with the anticancer drug mitoxantrone (MTO).
METHODS
Plasma and tissue distribution profiles of LHRH receptor-targeted MTO-loaded liposomes (LHRH-MTO-LIPs) were quantified in healthy mice or a xenograft tumor nude mouse model of MCF-7 breast cancer, and were compared with non-targeted liposomes and a free-drug solution.
RESULTS
The LHRH-MTO-LIPs demonstrated a superior pharmacokinetic profile relative to free MTO. The first target site of accumulation is the kidney, followed by the liver, and then the tumor; maximal tumor accumulation occurs at 4 h post-administration. Moreover, the LHRH-MTO-LIPs exhibited enhanced inhibition of MCF-7 breast cancer cell growth in vivo compared with non-targeted MTO-loaded liposomes (MTO-LIPs) and free MTO.
CONCLUSION
The novel LHRH receptor-targeted liposome may become a viable platform for the future targeted treatment of cancer.
背景
先前的一项研究开发了一种新型的促黄体生成素释放激素（LHRH）受体靶向脂质体。本研究旨在进一步评估载有抗癌药物米托蒽醌（MTO）的 LHRH 受体靶向脂质体的药代动力学、生物分布和抗肿瘤疗效。
方法
在健康小鼠或 MCF-7 乳腺癌异种移植肿瘤裸鼠模型中定量检测 LHRH 受体靶向 MTO 载体制备的脂质体（LHRH-MTO-LIPs）的血浆和组织分布特征，并与非靶向脂质体和游离药物溶液进行比较。
结果
与游离 MTO 相比，LHRH-MTO-LIPs 表现出更优越的药代动力学特征。第一个蓄积的靶位是肾脏，其次是肝脏，然后是肿瘤；给药后 4 小时达到最大肿瘤蓄积。此外，与非靶向 MTO 载体制备的脂质体（MTO-LIPs）和游离 MTO 相比，LHRH-MTO-LIPs 表现出增强的抑制 MCF-7 乳腺癌细胞在体内生长的作用。
结论
新型 LHRH 受体靶向脂质体可能成为未来癌症靶向治疗的一种可行平台。
Zotero 插件