基于单分散纳米羟基磷灰石的荧光/CT/MRI活体生物成像探针的构建及其在肿瘤诊疗中的应用

Multi-modality bioimaging probe based on nanoparticles shows a great potential in the field of cancer diagnosis and therapy. In this proposal, a simple method will be developed to establish a triple-modality in-vivo bioimaging probe for cancer diagnosis and therapy based on biocompatible nano-hydroxyapatite (nHA), where Ba2+ is chosen to dope into the lattice of nHA as a CT imaging agent to avoid the potential risk of commonly used Gd3+ and multi-functional near infrared emission quantum dots are loaded (tumor-recognition function, Mn2+ for MRI imaging and quantum dots for near infrared imaging) onto nHA to simultaneously obtain the tumor-targeting and imaging capability. We believe the results of this proposal will provide technical basis for the fabrication of other multi-modality bioimaging probe. Moreover, it will also be helpful for the protection of human health and for the promotion of nano-medicine in the field of clinical cancer diagnosis and therapy.

基于纳米粒子的多模态生物成像探针在癌症早期诊断和治疗领域具有广阔应用前景。本项目拟以单掺杂的方法，以Ba2+作为CT显影剂代替常用的Gd3+，避免Gd3+的潜在毒副作用，实现CT成像功能；同时，装载多功能（肿瘤识别功能、Mn2+的MRI成像功能以及量子点的近红外成像功能）近红外量子点，在装载量子点的同时即实现探针的肿瘤靶向性和多模态成像特性，发展基于nHA多模态活体生物成像探针的简便构建方法，并探索其应用于体内肿瘤的早期诊断与治疗的可能性。该方法的建立为基于其它生物相容性纳米粒子多模态成像探针的构建提供了技术基础，对于保障人类健康、促进临床肿瘤诊疗纳米医药的发展具有重要的科学意义和现实意义。

本研究以生物相容性良好的羟基磷灰石纳米粒子（Hydroxyapatite, HAp）和二氧化硅（Silica, SiO2）为载体，通过掺杂、交联、核壳结构等方式设计构建了一系列单模态、双模态生物成像探针和肿瘤诊疗平台，探索了其在体内外生物成像的应用前景。重点在水热法基础上发展了简单易行的构建具有良好肿瘤靶向特性和单分散性的HAp成像探针和肿瘤诊疗平台的方法，并通过核壳结构对CT信号的富集，以SiO2为载体构建了具有核壳结构的CT/FL双模态成像探针，实现了相同浓度下、特别是较低的探针浓度下优异的CT/FL双模态成像效果。上述探针和平台在肿瘤诊疗领域显示出一定应用前景，并为后续发展优化肿瘤诊疗探针及平台奠定了理论和实践基础。