Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma.
Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma.
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DOI：
10.1186/1477-3155-9-32
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发表时间：
2011-08-11
影响因子：
10.2
通讯作者：
Maake C
中科院分区：
文献类型：
--
作者：
Besic Gyenge E;Darphin X;Wirth A;Pieles U;Walt H;Bredell M;Maake C
头颈部鳞状细胞癌（HNSCC）目前是全球第八大癌症死亡原因。HNSCC的常规疗法的通常严重的副作用、功能障碍和不利的美容结果促使人们寻求新的治疗策略，包括评估纳米技术以改善例如药物递送和癌症成像。虽然二氧化硅纳米粒子在生物医学应用方面有很大的希望，但尚未在HNSCC的背景下对其进行研究。因此，在本体外研究中，我们分析了200-300 nm核-壳二氧化硅纳米颗粒在人HNSCC细胞系UMB-SCC 745中的细胞毒性、摄取和细胞内命运，所述纳米颗粒包封具有羟基、氨丙基或PEG化表面修饰的荧光染料三（联吡啶）二氯化钌（II）（Ru@SiO2-OH、Ru@SiO2-NH 2、Ru@SiO2-PEG）。我们发现，在浓度为0.125 mg/ml时，所使用的纳米颗粒对UMB-SCC 745的增殖率没有统计学显著影响。共聚焦和透射电子显微镜显示Ru@SiO2-OH和Ru@SiO2-NH 2在30分钟内的细胞内外观。它们被内化为单个纳米颗粒（可能通过网格蛋白包被的凹坑）或成簇，并且总是定位于细胞质膜结合的囊泡。免疫细胞化学共定位研究表明，这些纳米颗粒中只有一小部分被转移到早期的内体，而大部分积累在大的细胞器。从未观察到Ru@SiO2-OH和Ru@SiO2-NH 2纳米颗粒运输到溶酶体区室，而是在细胞分裂时繁殖。因此，Ru@SiO2-OH和Ru@SiO2-NH 2的细胞内持久性在5次细胞传代中可追踪，但没有导致细胞形态和活力的明显变化。与Ru@SiO2-OH和Ru@SiO2-NH 2相比，Ru@SiO2-PEG的吸收即使在24小时后也是最小的。我们的研究是第一个提供证据表明，基于二氧化硅的纳米颗粒可以作为HNSCC新的治疗选择的发展有用的工具。它们的长细胞内持久性对于例如慢性治疗方式可能是有利的。然而，其复杂的内吞途径需要进一步的调查。
Head and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridine)ruthenium(II) dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO2-OH, Ru@SiO2-NH2, Ru@SiO2-PEG) in the human HNSCC cell line UMB-SCC 745. We found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO2-OH and Ru@SiO2-NH2 within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits) or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO2-OH and Ru@SiO2-NH2 nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO2-OH and Ru@SiO2-NH2 was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO2-OH and Ru@SiO2-NH2 uptake of Ru@SiO2-PEG was minimal even after 24 h. Our study is the first to provide evidence that silica-based nanoparticles may serve as useful tools for the development of novel treatment options in HNSCC. Their long intracellular persistence could be of advantage for e.g. chronic therapeutic modalities. However, their complex endocytotic pathways require further investigations.
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影响因子：
3.7
作者：
Chen, M;von Mikecz, A
通讯作者：
von Mikecz, A
影响因子：
3.8
作者：
Kelm, JM;Timmins, NE;Nielsen, LK
通讯作者：
Nielsen, LK
DOI：
10.1016/j.jvir.2010.02.027
发表时间：
2010-08-01
影响因子：
2.9
作者：
French, J. Tyler;Goins, Beth;Bao, Ande
通讯作者：
Bao, Ande
影响因子：
10.8
作者：
Huang, Yiming;Swarup, Vimal P.;Bishnoi, Sandra Whaley
通讯作者：
Bishnoi, Sandra Whaley
影响因子：
11.4
作者：
Chang, Jenq-Sheng;Chang, Ke Liang B.;Kong, Zwe-Ling
通讯作者：
Kong, Zwe-Ling