Evaluation of poly (glycerol-adipate) nanoparticle uptake in an In Vitro 3-D brain tumor co-culture model

被引:35
作者
Meng, W.
Kallinteri, P.
Walker, D. A.
Parker, T. L.
Garnett, M. C.
机构
[1] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England
[2] Queens Med Ctr, Sch Human Dev, Nottingham NG7 2UH, England
[3] Univ Nottingham, Sch Biomed Sci, Nottingham NG7 2RD, England
基金
英国生物技术与生命科学研究理事会;
关键词
biodegradable nanoparticles; medulloblastoma; organotypic culture;
D O I
10.3181/0612-RM-301
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite the inherent problems associated with in vivo animal models of tumor growth and metastases, many of the current in vitro brain tumor models also do notaccurately mimic tumor-host brain interactions. Therefore, there is a need to develop such co-culture models to study tumor biology and, importantly, the efficacy of drug delivery systems targeting the brain. So far, few investigations of this nature have been published. In this paper we describe the development of a new model system and its application to drug delivery assessment. For our new model, a co-culture of DAOY cell brain tumor aggregates and organo-typic brain slices was developed. Initially, the DAOY aggregates attached to cerebellum slices and invaded as a unit. Single cells in the periphery of the aggregate detached from the DAOY aggregates and gradually replaced normal brain cells. This invasive behavior of DAOY cells toward organotypic cerebellum slices shows a similar pattern to that seen in vivo. A er validation of the co-culture model using transmission electron microscopy, nanoparticle (NP) uptake was then evaluated. Confocal micrographs illustrated that DAOY cells in this co-culture model took up most of the NPs, but few NPs were distributed into brain cells. This finding corresponded with results of NP uptake in DAOY and brain aggregates reported elsewhere.
引用
收藏
页码:1100 / 1108
页数:9
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