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适用于药物递送的磁性纳米颗粒的细胞摄取及体外毒性

Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery.

作者信息

Häfeli Urs O, Riffle Judy S, Harris-Shekhawat Linda, Carmichael-Baranauskas Anita, Mark Framin, Dailey James P, Bardenstein David

机构信息

Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada.

出版信息

Mol Pharm. 2009 Sep-Oct;6(5):1417-28. doi: 10.1021/mp900083m.

Abstract

Magnetic targeting is useful for intravascular or intracavitary drug delivery, including tumor chemotherapy or intraocular antiangiogenic therapy. For all such in vivo applications, the magnetic drug carrier must be biocompatible and nontoxic. In this work, we investigated the toxic properties of magnetic nanoparticles coated with polyethylenoxide (PEO) triblock copolymers. Such coatings prevent the aggregation of magnetic nanoparticles and guarantee consistent magnetic and nonmagnetic flow properties. It was found that the PEO tail block length inversely correlates with toxicity. The nanoparticles with the shortest 0.75 kDa PEO tails were the most toxic, while particles coated with the 15 kDa PEO tail block copolymers were the least toxic. Toxicity responses of the tested prostate cancer cell lines (PC3 and C4-2), human umbilical vein endothelial cells (HUVECs), and human retinal pigment epithelial cells (HRPEs) were similar. Furthermore, all cell types took up the coated magnetic nanoparticles. It is concluded that magnetite nanoparticles coated with triblock copolymers containing PEO tail lengths of above 2 kDa are biocompatible and appropriate for in vivo application.

摘要

磁靶向对于血管内或腔内给药很有用,包括肿瘤化疗或眼内抗血管生成治疗。对于所有此类体内应用,磁性药物载体必须具有生物相容性且无毒。在这项工作中,我们研究了涂覆有聚环氧乙烷(PEO)三嵌段共聚物的磁性纳米颗粒的毒性特性。这种涂层可防止磁性纳米颗粒聚集,并保证一致的磁性和非磁性流动特性。研究发现,PEO尾段长度与毒性呈负相关。PEO尾段最短为0.75 kDa的纳米颗粒毒性最大,而涂覆有15 kDa PEO尾段共聚物的颗粒毒性最小。所测试的前列腺癌细胞系(PC3和C4-2)、人脐静脉内皮细胞(HUVEC)和人视网膜色素上皮细胞(HRPE)的毒性反应相似。此外,所有细胞类型都摄取了涂覆的磁性纳米颗粒。结论是,涂覆有PEO尾段长度大于2 kDa的三嵌段共聚物的磁铁矿纳米颗粒具有生物相容性,适合体内应用。

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