Targeting of albumin-embedded paclitaxel nanoparticles to tumors.

Targeting of albumin-embedded paclitaxel nanoparticles to tumors.
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DOI:
10.1016/j.nano.2008.07.007
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发表时间:
2009-03
影响因子:
5.4
通讯作者:
Ruoslahti, Erkki
Ruoslahti, Erkki
中科院分区:
医学2区
文献类型:
--
作者:
Karmali, Priya Prakash;Kotamraju, Venkata Ramana;Kastantin, Mark;Black, Matthew;Missirlis, Dimitris;Tirrell, Matthew;Ruoslahti, Erkki

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我们已经使用肿瘤归巢肽靶向abraxane,一种临床批准的紫杉醇-白蛋白纳米颗粒,小鼠肿瘤。用两种肽CREKA和LyP-1(CGQKRTRGC)完成靶向。当静脉注射到携带MDA-MB-435人癌异种移植物的小鼠中时,荧光素(FAM)标记的CREKA-abraxane在肿瘤血管中积累,形成含有红细胞和纤维蛋白的聚集体。FAM-LyP-1-abraxane与表达其受体p32的血管外岛屿共定位。携带归巢肽和不同亚基上的标记的自组装混合胶束在与LyP-1-abraxane相同的肿瘤区域中积累,表明Lyp-1可以将完整的纳米颗粒递送到血管外部位。非靶向的FAM-abraxane在肿瘤组织中以微弱的网状结构形式被检测到。与未靶向的abraxane相比,LyP-1-abraxane产生了统计学上高度显著的肿瘤生长抑制。这些结果表明,纳米颗粒可以有效地靶向血管外肿瘤组织,并且靶向可以增强治疗性纳米颗粒的活性。
We have used tumor-homing peptides to target abraxane, a clinically approved paclitaxel-albumin nanoparticle, to tumors in mice. The targeting was accomplished with two peptides, CREKA, and LyP-1 (CGQKRTRGC). Fluorescein (FAM)-labeled CREKA-abraxane, when injected intravenously into mice bearing MDA-MB-435 human cancer xenografts, accumulated in tumor blood vessels, forming aggregates that contained red blood cells and fibrin. FAM-LyP-1-abraxane co-localized with extravascular islands expressing its receptor, p32. Self-assembled mixed micelles carrying the homing peptide and the label on different subunits accumulated in the same areas of tumors as LyP-1-abraxane, showing that Lyp-1 can deliver intact nanoparticles into extravascular sites. Untargeted, FAM-abraxane was detected in the form of a faint meshwork in tumor interstitium. LyP-1-abraxane produced a statistically highly significant inhibition of tumor growth compared to untargeted abraxane. These results show that nanoparticles can be effectively targeted into extravascular tumor tissue and that targeting can enhance the activity of a therapeutic nanoparticle.
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发表时间: 2008-09-01
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影响因子: 11.2
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发表时间: 2007-01-16
影响因子: 11.1
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发表时间: 2008-05-05
期刊: ADVANCED MATERIALS
影响因子: 29.4
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