Towards Ideal Magnetofluorescent Nanoparticles for Bimodal Detection of Breast-Cancer Cells
Towards Ideal Magnetofluorescent Nanoparticles for Bimodal Detection of Breast-Cancer Cells
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DOI：
10.1002/smll.200900881
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发表时间：
2009-11-16
期刊：
影响因子：
13.3
通讯作者：
Prosperi, Davide
中科院分区：
文献类型：
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作者：
Corsi, Fabio;De Palma, Clara;Prosperi, Davide
近年来，越来越多的基于纳米材料的新型肿瘤诊断分子标记物被开发出来。许多努力集中在实现位点靶向的生物缀合纳米颗粒上。相比之下，毒性、内吞作用和降解途径的机制仍然知之甚少，尽管它们对于临床转化至关重要。在这项研究中，三个不同的模型纳米磁荧光粒子系统（MFN）的设计和制造。这些纳米粒子的大小，形态，zeta电位，荧光效率，增强水质子的T-2弛豫的能力，和稳定性方面进行了评估。因此，开发了两种，并研究了MCF-7腺癌细胞中的内化机制、细胞内命运和毒性。除了有据可查的尺寸效应之外，阴离子电荷似乎是颗粒内化的关键因素，因为MFN通过细胞膜的渗透可以通过表面电荷来调制。透射电子显微镜结合共聚焦显微镜证据的超微结构分析表明，MFN是由网格蛋白介导的内吞和巨胞饮内化。此外，在EEA 1阳性内体和溶酶体中发现MFN，表明它们遵循内吞作用的生理途径。磁弛豫分析表明，在用低至30 μ g mL（-1）的粒子剂量处理后，MFN能够检测5 × 10（5）个细胞mL（-1）。因此，MFN似乎是一种有价值的和安全的双峰造影剂，可以开发用于乳腺癌的非侵入性诊断。
An increasing number of novel molecular markers based on nanomaterials for tumor diagnostics have been developed in recent years. Many efforts have focused on the achievement of site-targeted bioconjugated nanoparticles. In contrast, the mechanisms of toxicity, endocytosis, and degradation pathways are still poorly understood, despite their primary importance for clinical translation. In this study, three different model nanoscale magnetofluorescent particle systems (MFNs) are designed and fabricated. These nanoparticles are evaluated in terms of size, morphology, zeta potential, fluorescence efficiency, capability of enhancing T-2 relaxivity of water protons, and stability. Accordingly, two are developed and the mechanism of internalization, the intracellular fate, and the toxicity in MCF-7 adenocarcinoma cells are studied. Besides the well-documented size effect, the anionic charge seems to be a crucial factor for particle internalization, as MFN penetration through the cell membrane could be modulated by surface charge. Ultrastructural analysis of transmission electron micrographs combined with evidence from confocal microscopy reveals that MFNs are internalized by clathrin-mediated endocytosis and macropinocytosis. Moreover, MFNs are found in EEA1-positive endosomes and in lysosomes, indicating that they follow a physiological pathway of endocytosis. Magnetorelaxometric analysis demonstrates that MFNs enable the detection of 5 x 10(5) cells mL(-1) after treatment with particle dosages as low as 30 mu g mL(-1). Hence, MFNs appear to be a valuable and safe bimodal contrast agent that can be developed for the noninvasive diagnosis of breast cancer.