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通过优化基于脂质体的网状内皮系统(RES)阻断策略提高肿瘤摄取

Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy.

作者信息

Sun Xiaolian, Yan Xuefeng, Jacobson Orit, Sun Wenjing, Wang Zhantong, Tong Xiao, Xia Yuqiong, Ling Daishun, Chen Xiaoyuan

机构信息

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland 20892, United States.

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland 20892, United States.

出版信息

Theranostics. 2017 Jan 1;7(2):319-328. doi: 10.7150/thno.18078. eCollection 2017.

DOI:10.7150/thno.18078
PMID:28042337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5197067/
Abstract

Minimizing the sequestration of nanomaterials (NMs) by the reticuloendothelial system (RES) can enhance the circulation time of NMs, and thus increase their tumor-specific accumulation. Liposomes are generally regarded as safe (GRAS) agents that can block the RES reversibly and temporarily. With the help of positron emission tomography (PET), we monitored the tissue distribution of Cu-labeled 40 × 10 nm gold nanorods (Au NRs) after pretreatment with liposomes. We systematically studied the effectiveness of liposome administration by comparing (1) differently charged liposomes; (2) different liposome doses; and (3) varying time intervals between liposome dose and NR dose. By pre-injecting 400 μmol/kg positively charged liposomes into mice 5 h before the Au NRs, the liver and spleen uptakes of Au NRs decreased by 30% and 53%, respectively. Significantly, U87MG tumor uptake of Au NRs increased from 11.5 ± 1.1 %ID/g to 16.1 ± 1.3 %ID/g at 27 h post-injection. Quantitative PET imaging is a valuable tool to understand the fate of NMs and cationic liposomal pretreatment is a viable approach to reduce RES clearance, prolong circulation, and improve tumor uptake.

摘要

使纳米材料(NMs)被网状内皮系统(RES)截留的程度最小化,可以延长NMs的循环时间,从而增加它们在肿瘤部位的特异性蓄积。脂质体通常被视为安全(GRAS)制剂,能够可逆且暂时地阻断RES。借助正电子发射断层扫描(PET)技术,我们监测了用脂质体预处理后铜标记的40×10纳米金纳米棒(Au NRs)的组织分布情况。我们通过比较(1)不同电荷的脂质体;(2)不同的脂质体剂量;以及(3)脂质体给药剂量与纳米棒给药剂量之间不同的时间间隔,系统地研究了脂质体给药的效果。在注射Au NRs前5小时给小鼠预先注射400μmol/kg带正电荷的脂质体,Au NRs在肝脏和脾脏中的摄取量分别下降了30%和53%。值得注意的是,在注射后27小时,U87MG肿瘤对Au NRs的摄取量从11.5±1.1 %ID/g增加到了16.1±1.3 %ID/g。定量PET成像对于了解纳米材料的去向是一种有价值的工具,而阳离子脂质体预处理是减少RES清除、延长循环时间并提高肿瘤摄取量的一种可行方法。

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