光子上转换纳米光敏剂及其在癌症靶向可视化诊治中的关键科学问题

It is challenge that major diseases such as cancr can hardly be well diagnosed and therapy at early stage, for this purpose, based on the the advantages of photo-upconversion nanoparticales as carriers for photosensitizers and principle of fluorescence resonant energy transfer, the techonology of controlling preparation of nanomaterial and our early research fundamental, the photo-upconversion novel nanosructure with multifunctional shell/core is going to be constructed and studied for revealing relationshipes between the transport, transfer, excitation and emission of photo-energy and photo-upconversion effeciency, aming at the upcnversion nanocarriers with high photo-upconversion effeicency, and is going to study the relationshipes between the fluorescnece resonant energy transfer of the nanocarrier and photosensitizer and the yield of singlet oxygen production, to study effects of interaction btween the conjugation of upconversion nanocarrier and photosensitizer on the targeting sensitivity and specificity of diagnosis and visualization therapy of cancer, and to study the efficacy relationshipes of the interation between the molecules in vivo whole blood and the nano-photosensitizers to the targeting diagnosis and visualization therapy of cancer. Three key questions are expected to be answered with this project, i.e. the limitaion of low photo-upconversion efficiency of nanoparticles, the low targeting sensitivity and specificity of diagnosis and visualization therapy of cancer resulting from the interaction between "rigid" sufface of nanocarrier and anti-body molecules, effects of in vivo dynamic whole blood on the specificity and efficacy of nano-photosensitizers to realize the research object for novel approach in enhancing the photoupconversion efficiency of nanocarriers, to develop the novel method and thechonology in targeting diagnosis and visualization therapy of cancer based on highly efficient nano-photosensitizers.

针对癌症光动力早期诊治技术中关键难题，基于光子上转换纳米光敏载体优势及荧光共振能传递原理、纳米可控制备和研究前期基础，研究构筑的光子上转换纳米载体核壳新结构与光子能转换输运、传递、激发和上转换效率的关系；研究纳米载体与光敏分子之间的光子能量传递与单线态氧产率的关系；研究纳米光敏剂与耦联抗体分子的相互作用及其对靶向灵敏度和特异性的影响；研究靶向纳米光敏剂与体内全血相互作用及其对靶向可视化诊治功效的关系。重点解决制约光子能量上转换效率低、上转换纳米载体"刚性"表面与抗体分子相互作用导致导向灵敏度和特异性降低以及上转换光敏剂与体内动态血液分子的相互作用对特异靶向和功效的关系三个关键科学问题，实现提高光子能量上转换效率的普适性的新途径，发展基于高功效光子上转换纳米光敏剂的癌症靶向可视化诊治一体化新方法与新技术的研究目标。

针对癌症光动力早期诊治技术中关键难题，基于光子上转换纳米光敏载体优势及荧光共振能传递原理、纳米可控制备和研究前期基础，研究了构筑的光子上转换纳米载体核壳新结构与光子能转换输运、传递、激发和上转换效率的关系、纳米载体与光敏分子之间的光子能量传递与单线态氧产率的关系、纳米光敏剂与耦联抗体分子的相互作用及其对靶向灵敏度和特异性的影响、靶向纳米光敏剂与体内全血相互作用及其对靶向可视化诊治功效的关系。重点解决了制约光子能量上转换效率低、上转换纳米载体"刚性"表面与抗体分子相互作用导致导向灵敏度和特异性降低以及上转换光敏剂与体内动态血液分子的相互作用对特异靶向和功效的关系三个关键科学问题，实现提高光子能量上转换效率的普适性的新途径，发展基于高功效光子上转换纳米光敏剂的癌症靶向可视化诊治一体化新方法与新技术的研究目标。. 本项目发表SCI论文16篇，申请发明专利7项，培养博士研究生8人，硕士研究生3人。