纳米颗粒血液滞留时间以及从血液循环选择性进入靶组织的效率是影响纳米药物诊疗效果的两大要素。我们前期通过噬菌体展示技术发现了能延长纳米颗粒血液滞留时间的延时肽以及能减少稀土纳米颗粒与组织细胞相互作用的表面涂层肽。本项目拟在现有工作基础上，以金纳米颗粒、氧化钆纳米颗粒、工程化M13噬菌体以及聚磷酸酯-聚已内酯有机高聚物纳米药物载体为模式材料，在相应动物模型中研究延时肽、表面涂层肽以及组织靶向肽的多重组合修饰延长纳米颗粒血液滞留时间、优化纳米颗粒组织器官分布以及提高纳米颗粒诊疗效果的效应，并从纳米颗粒与血液循环系统相互作用的角度出发，阐明延时肽和表面涂层肽调控纳米颗粒体内滞留分布的生物学及力学机制。本项目旨在通过上述研究，有效解决诊疗用纳米颗粒体内应用中的瓶颈问题，实现提高诊疗效果及降低毒副作用的终极目标。

Prolonged blood retention time and effective penetration into the target tissue are two of the key factors that determine the efficacy of theranostic nanoprticles. We have discovered, through innovative use of the phage display approach, a blood circulation-prolonging peptide for nanoparticles and a surface-coating peptide for rare earth nanomaterials. In this project we will study the effect of a variety of peptide modifications, including modifications with the circulation-prolonging peptide or the surface-coating peptide alone and in combinations with tissue-homing peptides, on the blood retention time, biodistribution and theranostic efficacy of selected nanoparticles. The nanoparticles selected for this study include gold nanoparticles (for CT imaging and photothemal therapy), gadolinium oxide nanoprticles (for MRI imaging), PCL-PPEEA polymeric nanoparticles (for siRNA-mediated anti-cancer therapy) and engineered M13 phage (for anti-bacterial therapy). We will also investigate the mechanism through which the circulation-prolonging peptide and the surface-coating peptide interact with the blood circulatory system. Our work addresses the bottleneck issues faced by many in vivo applications and may lead to improved biosafety and efficacy for theranostic nanoparticles.