Interactions of hydrophobic and hydrophilic semiconductor quantum dots with cell model systems for liver and adipose tissue (NANOFATE)

半导体量子点和超顺磁性氧化铁纳米晶(SPIO)具有特殊的物理性质，非常适合在体外和体内的生物医学应用。直接注射纳米晶体用于成像和治疗是未来进入人类的一条重要途径。因此，仔细研究人体对纳米晶体的生物反应是至关重要的，以避免有害的副作用。近年来，我们建立了一套系统来制备具有亲水性或疏水性的纳米晶，这些纳米晶在体外和体内的生物条件下都能存活下来。这些颗粒对肝脏和脂肪组织细胞模型系统中细胞内过程的影响已经在第一个资助期内进行了研究，但尚不清楚这些发现是否能转化为活体情况。目前应用的目标是在体内研究纳米晶体的相互作用、加工和降解，以及注射纳米晶体后小鼠对这些相互作用的特定细胞反应。为了解决这些问题，我们将·确定不同类型的肝细胞对纳米晶体清除的贡献。·在肝细胞内跟踪纳米晶体的细胞内路线。·量化纳米晶体的降解和排泄。·探索与细胞类型和肝脏细胞内定位相关的对纳米晶体的生物反应。这些结果不仅将为与纳米晶体意外暴露相关的潜在危险提供深入的见解，还将极大地影响纳米晶体在生物医学应用中的潜在使用。

Semiconductor quantum dots (QDs) and superparamagnetic iron-oxide nanocrystals (SPIOs) have exceptional physical properties that are well-suited for biomedical applications in vitro and in vivo. The direct injection of nanocrystals for imaging and therapy represents an important entry route into humans in future. Therefore, it is crucial to carefully investigate the biological response of the body to nanocrystals to avoid harmful side effects. In recent years we established a system to prepare nanocrystals with hydrophilic or hydrophobic properties which survive biological conditions in vitro and in vivo. The impact of these particles on intracellular processes in cell model systems for liver and adipose tissues have been investigated within the first funding period but it still remains unclear whether these findings can be translated to the situation in vivo.The goal of the current application is to investigate in vivo the interaction, processing and degradation of nanocrystals as well as the specific cellular response to these interactions after injection of nanocrystals in mice. To address these issues we will• determine the contributions of different hepatic cell types for nanocrystals clearance.• Follow the intracellular routes of nanocrystals within hepatic cells.• quantify the degradation and excretion of nanocrystals.• explore biological responses to nanocrystals in relation to cell type and intracellular localization in the liver.The outcome of these results will not only provide in depth insights into potential hazards associated with unintended exposure of nanocrystals but will also greatly influence the potential use of nanocrystals for biomedical applications.