Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy.

Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy.
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通过优化基于脂质体的 RES 封锁策略提高肿瘤摄取

DOI:
10.7150/thno.18078
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发表时间:
2017
期刊:
影响因子:
12.4
通讯作者:
Chen X
Chen X
中科院分区:
医学1区
文献类型:
--
作者:
Sun X;Yan X;Jacobson O;Sun W;Wang Z;Tong X;Xia Y;Ling D;Chen X

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通过网状内皮系统(RES)最大限度地减少纳米材料(NM)的隔离可以增加NM的循环时间,从而增加其肿瘤特异性积聚。脂质体通常被认为是安全的(GRAS)药物,可以可逆地和暂时地阻断RES。利用正电子发射断层扫描(PET)技术,观察了脂质体预处理后64 Cu标记的40 × 10 nm金纳米棒(Au NRs)在体内的组织分布。我们通过比较(1)不同电荷的脂质体;(2)不同的脂质体剂量;(3)脂质体剂量和NR剂量之间的不同时间间隔,系统地研究了脂质体给药的有效性。在注射Au NRs前5 h预先注射400 μmol/kg荷正电脂质体,小鼠肝脏和脾脏对Au NRs的摄取分别减少30%和53%。显著地,U87 MG肿瘤对Au NR的摄取在注射后27小时从11.5 ± 1.1% ID/g增加到16.1 ± 1.3% ID/g。定量PET成像是了解NM在体内命运的有价值的工具,阳离子脂质体预处理是减少RES清除、延长循环和改善肿瘤摄取的可行方法。
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 in vivo tissue distribution of 64Cu-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 in vivo and cationic liposomal pretreatment is a viable approach to reduce RES clearance, prolong circulation, and improve tumor uptake.
超大无机光PET成像纳米粒子探针的临床翻译。
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