用于增强太赫兹活体成像对比度的靶向纳米造影技术

THz imaging contrast in living body has been limited severely, due to strong THz absorption of water. This project proposes to develop vanadium dioxide as a THz imaging contrast agent, which exhibits temperature induced insulator-metal phase transition characteristic. Mechanism for the phase transition induced enhancement of THz reflection in vanadium dioxide nanoparticles will be elucidated. And the phase transition temperature of vanadium dioxide will be decreased by doping, and so the phase transition would be triggered by abnormal temperature rising in lesion region. On the other hand, a polymer target carrier will be designed for loading vanadium dioxide nanoparticles and delivering them to target imaging area in living body. Subsequently, the THz in vivo imaging will be carried out in tumor-bearing mice. The effect of vanadium dioxide loaded by polymer target carrier on the improvement of THz imaging contrast will be investigated. This project would develop a new THz imaging contrast agent, and promote its application in in vivo THz imaging.

太赫兹波对水强烈吸收，导致其生物活体成像对比度降低，从而极大限制了太赫兹波在生物成像诊断领域的研究和应用。本项目提出利用二氧化钒在热致绝缘-金属相变过程中对太赫兹波反射信号增强的特性，发展可对生物病灶温度响应的太赫兹活体成像纳米造影材料。项目将研究二氧化钒纳米颗粒相变过程中对太赫兹波反射信号的增强机制，并通过材料设计制备对增强效果加以优化；通过掺杂等方式降低二氧化钒的相变温度至病灶区域温度附近，同时改善相变对温度的敏感性；设计可以负载二氧化钒纳米颗粒的高分子靶向载体，研究靶向造影体系的生物相容性及其在生物体内的分布、释放特性；在此基础上，以荷瘤小鼠为动物模型，开展利用靶向造影体系对病灶区域温度响应进而增强太赫兹成像对比度的实验研究，探索该技术在生物活体成像和诊断方面的应用前景。本研究有望发展一种新型太赫兹造影材料和技术，完善太赫兹成像造影体系，促进太赫兹波在医学成像和诊断方面的应用。

太赫兹波对水强烈吸收，导致其生物活体成像对比度降低，从而极大限制了太赫兹波在生物成像诊断领域的研究和应用。本项目以提高太赫兹活体成像对比度为目的，开展了多种太赫兹成像造影剂研究。采用原位搅拌水热法制备纳米VO2，通过W元素掺杂降低其相变温度，获得了纳米VO2颗粒相变温度随W元素掺杂量变化的规律；纳米VO2相变温度可调，实现了“相变温度在常规病灶区域温度附近”可调的目的，可利用病灶温度诱发纳米颗粒相变，增强太赫兹反射强度，最终实现成像对比度增强；以纳米金棒、黑色二氧化钛纳米颗粒为例，前列腺癌（PC3）细胞、小细胞肺癌（H1688）细胞为成像对象，验证了造影剂可有效提高生物目标的太赫兹成像对比度。进一步研究了太赫兹造影材料的细胞毒性和靶向效果。该研究获得了多种可用于太赫兹活体成像的纳米造影材料，成果发表于Journal of biomedical nanotechnology、Applied Physics Letters、ACS Applied Materials & Interfaces等期刊，并获授权国内首件太赫兹生物成像造影剂专利。