基于高通量纳米安全性评价系统的金纳米材料构效关系研究

Safety evaluation of engineered nanomaterials is becoming a worldwide problem. Developing high-throughput screening system as primary platform to replace the traditional animal model-based testing is emerging as an alternative strategy for assessment of nanosafety to respond to dramatic increase in engineered nanomaterials production. Reveal the qualitative relationship between characteristic and potential risk of nanomaterial is helpful to use and design safer nano-products. In this proposal, we plan to build a high-throughput system for synthesizing nanomaterials and testing their nanotoxicity. The system will combine a high-throughput synthesis platform which based on microfluidics and a high-throughput nanotoxicity-testing system. Using the system, gold nanoparticles with typical characteristics at nanoscale will be synthesized systematically, their cytotoxic mechanism would be comprehensive analysed through multiple toxicological parameters, and the basic prediction model for nanosafety of gold is expected to be established. This study provides new approach for studying the "structure-activity" relationship of nanomaterials. It is expected that assessing health risk of gold nanomaterials will not only be helpful for further development of these widely used materials for clinical applications, but also pave a new avenue for high-throughput evaluation of nanotoxicity issue of other nanomaterials.

随着纳米产品市场的急剧扩大，纳米技术潜在的环境、健康和安全风险日益突出。应对纳米材料安全性高效评价这一新的挑战，亟需以高通量的标准毒理学检测体系代替传统动物初级筛选平台，并建立纳米材料典型特征与其潜在健康风险间的定性对应关系。针对上述问题，本项目拟利用基于微流体的纳米材料高通量可控合成平台，结合基于多参数毒理学检测与荧光分析的高通量细胞毒性研究平台，创新性地构建高通量纳米安全性体外评价系统；利用该体系，以目前应用广泛的金纳米材料为研究对象，通过系统制备具有各种物理化学性质的金纳米材料，并高通量分析其细胞毒效应指纹，系统研究金纳米材料的细胞损伤机制和毒理学"结构-效应"关系，建立基于材料典型特征的金纳米材料安全性初级预测模型。本课题有望对给定参数的金纳米材料实现初步风险评估，从而为金纳米材料的生物医学安全应用提供科学的指导，并进一步为更广泛的纳米药物的设计与筛选提供新的方法与思路。

随着纳米技术对生物医药等领域发展的巨大推动作用日益显露，纳米材料对人类健康的影响及其安全性评价在世界范围内受到极大关注，亟需建立纳米材料典型特征与其生物效应间的构效关系。本项目以具有良好生物医用前景的金纳米材料为研究对象，系统构建了具有典型物理化学特征的金纳米材料库。利用多参数毒理学检测方法，全面研究了各种金纳米材料的细胞生物学效应，证实金纳米材料是一种相对较为安全的工程纳米材料。基于初步风险评估，筛选了具有突出生物相容性的核壳结构金纳米材料，重点探索了它们的生物医学构效关系。研究揭示了材料长径比对棒状纳米金壳的细胞摄取、血管渗透及肿瘤分布的影响规律，阐明了调控纳米金棒局域电场提高光敏剂量子产率的内在机制，强调了合理的构效关系设计在增强纳米生物医学效应中的重要性。本项目研究结果将为金纳米材料的生物医学安全应用以及更广泛的纳米药物的设计与筛选提供科学依据。