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In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice following skin application post-ultraviolet radiation

机译:紫外线照射后皮肤施用后C57BL / 6无毛小鼠中量子点全身转运的体内定量

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BackgroundPrevious work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360?mJ/cm2 UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model. ResultsResults indicate that QDs can penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased cadmium in the local lymph nodes of all QD treated mice. The average % recovery for all treatment groups was 69.68% with ~66.84% of the applied dose recovered from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the applied dose was recovered from the lymph nodes across various treatment groups. When QDs are applied 4?days post UV irradiation, at the peak of the skin barrier defect and LC migration to the local lymph node, there is an increased cellular presence of QD in the lymph node; however, AAS analysis of local lymph nodes display no difference in cadmium levels due to UVR treatment. ConclusionsOur data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport to the lymph node may occur by both cellular (dendritic and macrophage) and non-cellular mechanisms. It is interesting that these specific nanoparticles were retained in skin similarly regardless of UVR barrier disruption, but the observed skin immune cell interaction with nanoparticles suggest a potential for immunomodulation, which we are currently examining in a murine model of skin allergy.
机译:背景技术先前的研究证明了纳米粒子的大小,表面电荷和与皮肤屏障有关的渗透性进入小鼠皮肤的可行层。这项工作的目的是表征有无紫外线辐射(UVR)引起的皮肤屏障破坏的组织分布和纳米粒子向皮肤外转运的机制。用原子吸收光谱法(AAS),流式细胞术和共聚焦显微镜检查了UVR剂量(180和360?mJ / cm 2 UVB)对皮肤渗透和量子点全身分布的影响( QD)纳米粒子使用无毛C57BL / 6小鼠模型在UVR后的不同时间点局部应用。结果结果表明,QDs可以穿透小鼠皮肤,而不管UVR暴露如何,所有QD治疗的小鼠的局部淋巴结中镉的增加证明了这一点。所有治疗组的平均恢复百分比为69.68%,从皮肤(表皮和皮内)恢复的剂量约为〜66.84%。从各个治疗组的淋巴结中平均回收到平均0.024%的应用剂量。当在紫外线照射后4天使用QD时,在皮肤屏障缺损和LC迁移到局部淋巴结的高峰期,淋巴结中QD的细胞数量增加。然而,对局部淋巴结的AAS分析显示,由于UVR处理,镉水平没有差异。结论我们的数据表明,朗格汉斯细胞(LCs)可以吞噬皮肤中的QD,但通过细胞(树突状细胞和巨噬细胞)和非细胞机制均可发生向淋巴结的转运。有趣的是,无论UVR屏障是否被破坏,这些特定的纳米颗粒都可以类似地保留在皮肤中,但是观察到的与纳米颗粒的皮肤免疫细胞相互作用表明存在免疫调节的潜力,我们目前正在鼠类皮肤过敏模型中对其进行研究。

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