Evaluation of nanoparticle uptake in co-culture cancer models.

Evaluation of nanoparticle uptake in co-culture cancer models.
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DOI:
10.1371/journal.pone.0070072
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Correia IJ
Correia IJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Costa EC;Gaspar VM;Marques JG;Coutinho P;Correia IJ

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共培养模型目前正在弥合经典培养和体内动物模型之间的差距。探索这种新方法,通过建立癌症-基质协同相互作用,揭示了体外模拟肿瘤微环境的可能性。值得注意的是,这些器官型模型提供了一个完美的平台,用于以高通量筛选模式开发和临床前评估负载有抗肿瘤药物的候选纳米载体,成本较低,没有伦理问题。然而,到目前为止,该评价仅限于以精确的细胞比例建立的共培养系统,没有解决在不同肿瘤中常见的天然细胞异质性。因此,本文在含有不同细胞比率的各种成纤维细胞-MCF-7共培养系统中表征多功能纳米载体的效率,以揭示影响纳米载体性能和治疗结果的关键设计参数。不同细胞在培养物中的组织样分布证实了共培养模型的成功建立。在各种共培养系统中的纳米颗粒孵育揭示了这些纳米载体对癌细胞具有靶向特异性,表明它们适用于这种疾病治疗。此外,通过使用不同的共培养比率,获得不同的纳米颗粒摄取曲线。这些发现对于新药物递送系统的未来设计和优化至关重要,因为它们的真实的靶向能力必须在异源细胞群体中解决,例如在肿瘤中发现的那些。
Co-culture models are currently bridging the gap between classical cultures and in vivo animal models. Exploring this novel approach unlocks the possibility to mimic the tumor microenvironment in vitro, through the establishment of cancer-stroma synergistic interactions. Notably, these organotypic models offer a perfect platform for the development and pre-clinical evaluation of candidate nanocarriers loaded with anti-tumoral drugs in a high throughput screening mode, with lower costs and absence of ethical issues. However, this evaluation was until now limited to co-culture systems established with precise cell ratios, not addressing the natural cell heterogeneity commonly found in different tumors. Therefore, herein the multifunctional nanocarriers efficiency was characterized in various fibroblast-MCF-7 co-culture systems containing different cell ratios, in order to unravel key design parameters that influence nanocarrier performance and the therapeutic outcome. The successful establishment of the co-culture models was confirmed by the tissue-like distribution of the different cells in culture. Nanoparticles incubation in the various co-culture systems reveals that these nanocarriers possess targeting specificity for cancer cells, indicating their suitability for being used in this illness therapy. Additionally, by using different co-culture ratios, different nanoparticle uptake profiles were obtained. These findings are of crucial importance for the future design and optimization of new drug delivery systems, since their real targeting capacity must be addressed in heterogenous cell populations, such as those found in tumors.
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