Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice
Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice
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DOI：
10.1016/j.jconrel.2004.01.002
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发表时间：
2004-03-24
影响因子：
10.8
通讯作者：
Mumper, RJ
中科院分区：
文献类型：
--
作者：
Oyewumi, MO;Yokel, RA;Mumper, RJ
这些研究的目的是比较叶酸涂层和PEG涂层钆（Gd）纳米颗粒的细胞摄取，生物分布和肿瘤保留。Gd是一种很有潜力的肿瘤中子俘获治疗剂。钆纳米粒子是从水包油微乳液模板工程。为了获得叶酸包被的纳米颗粒，在纳米颗粒制剂中包括叶酸配体[通过PEG间隔物MW 3350化学连接至二硬脂酰磷脂酰乙醇胺（DSPE）的叶酸]。类似地，对照纳米颗粒用DSPE-PEG-MW 3350（PEG涂覆的）涂覆。纳米颗粒的特征在于基于大小，大小分布，形态，生物相容性和肿瘤细胞摄取。在KB（人鼻咽癌）荷瘤无胸腺小鼠中进行体内研究。在注射纳米颗粒（10 mg/kg）后，以预定的时间间隔进行生物分布和肿瘤保留研究。钆纳米粒子不聚集血小板或激活中性粒细胞。注射后8、16和24 h血液中纳米颗粒的保留分别为注射剂量（ID）的60%、13%和11%。达到了33 +/- 7 μ g Gd/g的最大Gd肿瘤定位。叶酸包被的和PEG包被的纳米颗粒具有相当的肿瘤蓄积。然而，叶酸包被的纳米颗粒的细胞摄取和肿瘤滞留显著增强PEG包被的纳米颗粒。因此，叶酸配体包被的益处是促进肿瘤细胞内化和Gd-纳米颗粒在肿瘤组织中的保留。工程化纳米颗粒可能具有肿瘤靶向递送Gd的潜力，从而提高NCT的治疗成功率。(C)2004 Elsevier B. V.保留所有权利。
The purpose of these studies was to compare the cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium (Gd) nanoparticles. Gd is a potential agent for neutron capture therapy (NCT) of tumors. Gd nanoparticles were engineered from oil-in-water microemulsion templates. To obtain folate-coated nanoparticles, a folate ligand [folic acid chemically linked to distearoylphosphatidylethanolamine (DSPE) via a PEG spacer MW 3350] was included in nanoparticle preparations. Similarly, control nanoparticles were coated with DSPE-PEG-MW 3350 (PEG-coated). Nanoparticles were characterized based on size, size distribution, morphology, biocompatibility and tumor cell uptake. In vivo studies were carried out in KB (human nasopharyngeal carcinoma) tumor-bearing athymic mice. Biodistribution and tumor retention studies were carried out at pre-determined time intervals after injection of nanoparticles (10 mg/kg). Gd nanoparticles did not aggregate platelets or activate neutrophils. The retention of nanoparticles in the blood 8, 16 and 24 h post-injection was 60%, 13% and 11% of the injected dose (ID), respectively. A maximum Gd tumor localization of 33 +/- 7 mug Gd/g was achieved. Both folate-coated and PEG-coated nanoparticles had comparable tumor accumulation. However, the cell uptake and tumor retention of folate-coated nanoparticles was significantly enhanced over PEG-coated nanoparticles. Thus, the benefits of folate ligand coating were to facilitate tumor cell internalization and retention of Gd-nanoparticles in the tumor tissue. The engineered nanoparticles may have potential in tumor-targeted delivery of Gd thereby enhancing the therapeutic success of NCT. (C) 2004 Elsevier B.V. All rights reserved.