Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; Luminomics Inc., Baltimore, MD 21286, USA.
Adv Drug Deliv Rev. 2019 Aug;148:344-359. doi: 10.1016/j.addr.2019.01.011. Epub 2019 Feb 12.
Several key attributes of zebrafish make them an ideal model system for the discovery and development of regeneration promoting therapeutics; most notably their robust capacity for self-repair which extends to the central nervous system. Further, by enabling large-scale drug discovery directly in living vertebrate disease models, zebrafish circumvent critical bottlenecks which have driven drug development costs up. This review summarizes currently available zebrafish phenotypic screening platforms, HTS-ready neurodegenerative disease modeling strategies, zebrafish small molecule screens which have succeeded in identifying regeneration promoting compounds and explores how intravital imaging in zebrafish can facilitate comprehensive analysis of nanocarrier biodistribution and pharmacokinetics. Finally, we discuss the benefits and challenges attending the combination of zebrafish and nanoparticle-based drug optimization, highlighting inspiring proof-of-concept studies and looking toward implementation across the drug development community.
几种关键的斑马鱼属性使它们成为发现和开发促进再生治疗方法的理想模型系统；最值得注意的是，它们具有强大的自我修复能力，这种能力延伸到中枢神经系统。此外，通过在活体脊椎动物疾病模型中直接进行大规模药物发现，斑马鱼克服了推动药物开发成本上升的关键瓶颈。这篇综述总结了目前可用的斑马鱼表型筛选平台、高通量筛选准备就绪的神经退行性疾病建模策略、成功鉴定促进再生化合物的斑马鱼小分子筛选，并探讨了活体成像在斑马鱼中的应用如何促进纳米载体生物分布和药代动力学的全面分析。最后，我们讨论了结合斑马鱼和基于纳米粒子的药物优化的好处和挑战，强调了鼓舞人心的概念验证研究，并展望了在整个药物开发社区中的实施。
