纳米药物载体对子代斑马鱼发育影响与生物安全性评价研究

With the rapid development of nanotechnology, the study on artificial nanoparticles play a significant role in biomedicine and functional imaging. Functional drug-carrier nanoparticles show a potential application on pharmacology, oncology and biomedicine. Thus, the multifunctionality and biocompatibility of novel nanoparticles should be carefully assessed for human health.To assure a responsible and sustainable growth of nanotechnology, the environmental health and safety aspect of engineered nanomaterials and nano-related products needs to be addressed at a rate commensurate with the expansion of nanotechnology. Zebrafish has been demonstrated as a correlative in vivo vertebrate model for such task. In addition to morphological and histopathological observations, the accessibility of gene manipulation would greatly empower such a model for detailed mechanistic studies of any nanoparticles of interest. The potential for establishing highthroughput screening platforms to facilitate the nanoparticle studies is highlighted. When we utilize the nanoparticles for medical treatments, the adverse effects of nanomaterials may be observed not only in the patients but also in their next generation. Especially for the pregnant women, the nanoparticles may leave a terrible influence on fetal development. Our previous study showed that chorion changes in developmental toxicity were induced by polymer microspheres in zebrafish embryos. In this study, We shall focus on several essential drug-carrier nanoparticles. With protein modification on the surface of nanomaterials, the multifunctionality on biomedicine should be proved at the cellular level. As for the biocompatibility, we hope to create a much more sensitive zebrafish model for testifying the toxicity of next generation growth and development. Meanwhile, the distribution in female zebrafish and larva need to be evaluated. For the potential mechanism of nanotoxicity, the zebrafish neural development and behavior influence should be explored. The study aims to establish a novel evaluation system to improve theoretical basis and experimental fundation for a wide variety of drug-vector nanoparticles.

随着纳米科学技术的快速发展，人工纳米材料的研究与开发在生物医药领域具有重要的价值。在此之中，功能性药物载体纳米材料因其潜在的应用前景而备受关注，而其多功能性和生物安全性评价则十分重要。纳米材料应用于人类所产生健康问题的影响，除了不仅涉及到应用者本身，也可能会影响到子代，尤其是孕期母体接受纳米材料对胎儿发育的影响。课题组前期研究证明通过改变斑马鱼绒毛膜结构可检测纳米材料的毒性，本课题主要研究几种重要的纳米结构药物载体，通过蛋白修饰等手段，在细胞水平上验证其生物医药功能；建立不同途径及方式的雌性斑马鱼纳米材料暴露模型，着重研究纳米材料暴露对子代斑马鱼发育的影响。同时，检测孕期暴露后，纳米材料在雌鱼和幼鱼体内的分布与聚集情况。探索纳米结构材料的特性和作用途径对斑马鱼神经发育和行为学影响及其潜在的机制。再者，为建立纳米材料安全性评价体系以及纳米药物载体的研制与改进提供理论依据与实验基础。

随着纳米科学技术的快速发展，人工纳米材料的研究与开发在生物医药领域具有重要的价值。在此之中，功能性药物载体纳米材料因其潜在的应用前景而备受关注，而其多功能性和生物安全性评价则十分重要。纳米材料应用于人类所产生健康问题的影响，除了不仅涉及到应用者本身，也可能会影响到子代，尤其是孕期母体接受纳米材料对胎儿发育的影响。课题组前期研究证明通过改变斑马鱼绒毛膜结构可检测纳米材料的毒性，本课题主要研究几种重要的纳米结构药物载体，通过蛋白修饰等手段，在细胞水平上验证其生物医药功能；建立不同途径及方式的雌性斑马鱼纳米材料暴露模型，着重研究纳米材料暴露对子代斑马鱼发育的影响。同时，检测孕期暴露后，纳米材料在雌鱼和幼鱼体内的分布与聚集情况。探索纳米结构材料的特性和作用途径对斑马鱼神经发育和行为学影响及其潜在的机制。再者，为建立纳米材料安全性评价体系以及纳米药物载体的研制与改进提供理论依据与实验基础。