有机红光近红外纳米材料在生物成像和载药中的应用

The development of precise bioimaging and drug delivery systems is one of the frontier and hot research field in bionanotechnology. Based on our research background in biological effects of fluorescent organic nanoparticles and biological nanomaterials, we proposed preparation of red/near-infrared organic nanomaterials and their application in bioimaging, drug targeting transport and delivery. Take advantage of the conjugated and electron-rich group of thiophene derivatives, we intend to synthesize novel red/near-infrared compounds with active end group like double bond. The mesoporous silica nanoparticles will be prepared by surfactant modification and sol-gel method of the compounds, and their bioimaging applications will be carried out due to their stabilized luminescent aggregates by the nanocomposites. Through size design of the nanopores of mesoporous molecular sieve, we can control and stabilize the degree of molecular aggregation, thereby precisely regulating the emission wavelength of the aggregates. In addition, the mercaptosuccinic acid modified mesoporous silica nanoparticles will be prepared by thiol-ene click reaction, and the efficient loading capacity and pH responsive release of cisplatin with the carboxyl group of mercaptosuccinic acid will also be investigated. This proposal is not only expected to significantly enhance the controllability, stability and predictability of organic fluorescent material in biological imaging and therapeutic applications, but also provide a new platform for the development of novel precise nano-diagnosis and treatment system.

发展精准的生物成像和给药体系是当今纳米生物材料研究的前沿。申请人基于前期在有机发光和生物纳米材料领域的工作，提出合成红光/近红外有机-无机纳米复合材料新思路，并探索该材料在生物成像和药物靶向输运及释放中的应用。我们选择新型的共轭噻吩类富电子核心官能团，合成具有双键末端基团的红光/近红外有机染料。通过溶胶凝胶方法，制备有机发光染料与介孔二氧化硅纳米复合材料。通过对纳米孔的尺寸设计，调控并稳定分子聚集程度，精准设计材料的发光效应。然后，利用“巯基-双键”点击反应将硫代苹果酸修饰到上述纳米复合材料中，再通过苹果酸羧基和传统抗癌药物顺铂的配位及pH响应性，实现纳米复合材料对顺铂药物的高效载带和响应性释放。此课题不仅有望显著增强有机聚集态荧光材料在生物成像和治疗应用中的可控、稳定和可预测性，同时也为发展新型精准纳米诊疗体系提供新的材料平台。

发展精准的生物成像和给药体系是当今纳米生物材料研究的前沿。申请人基于前期在有机发光和生物纳米材料领域的工作，提出合成红光/近红外有机-无机纳米复合材料新思路，并探索该材料在生物成像和药物靶向输运及释放中的应用。我们选择新型的共轭噻吩类富电子核心官能团，合成具有双键末端基团的红光/近红外有机染料。通过溶胶凝胶方法，制备有机发光染料与介孔二氧化硅纳米复合材料。通过对纳米孔的尺寸设计，调控并稳定分子聚集程度，精准设计材料的发光效应。然后，利用“巯基-双键”点击反应将硫代苹果酸修饰到上述纳米复合材料中，再通过苹果酸羧基和传统抗癌药物顺铂的配位及pH响应性，实现纳米复合材料对顺铂药物的高效载带和响应性释放。此课题为发展新型精准纳米诊疗体系提供新的材料平台。.通过共价，非共价键结合设计有机-无机复合材料的思路，我们相继报道了一系列新型精准纳米诊疗体系：包括聚集诱导发光染料和二氧化硅纳米粒子的非共价键结合制备复合材料、担载顺铂的PEG化介孔二氧化硅（SBA-15）聚合物复合材料、担载顺铂的含磷脂胆碱的共聚物直接表面接枝的介孔二氧化硅SBA-15聚合物复合材料、以FeBr3为光催化剂，衣康酸和2-甲基丙烯酰氧乙基磷酰胆碱为单体，采用亲水性共聚物改性介孔二氧化硅纳米粒子、聚集诱导发光染料和聚（2-乙基-2-恶唑啉）共载的介孔二氧化硅纳米粒子、具有pH响应性腙键的ND基复合材料等，其在恶性肿瘤化疗、光疗、成像方面显示出极强的应用能力，相关工作发表在《Applied Surface Science》、《Materials Science & Engineering C》、《Journal of Colloid and Interface Science》、《Macromolecular Chemistry and Physics》、《Applied Surface Science》、《Colloids and Surfaces B》等期刊上。