镱铥共掺氟化钙纳米晶/介孔氧化硅复合纤维药物载体的构建和评价

To tackle the funtional challenges of implantable localized drug delivery systems (LDDS), external release control and monitored release kinetics, based on the current principle of mesoporous structure forming mechanism and nanocrystal in situ growth phenomenon, we hereby propose a study to investigate a new type of CaF2:Tm,Yb@mSiO2 composite fiber LDDS, comprising of mesoporous silica fibers and Tm/Yb co-doped CaF2 nanocrystals within its mesopore channels, via sol-gel and electrospinning techniques. The influence of surfactants, precursor physical properties and electrospinning parameters on the mesoporous structure characteristics of silica fibers will be uncovered; The in situ growth mechanism of CaF2:Tm,Yb nanocrystals within the mesopores of silica nanofibers will be illustrated systematically, and the effect of microstructural characteristics of CaF2:Tm,Yb@mSiO2 fibers on its photoluminescent properties will be investigated; Furthermore, the relationship between the microstructure of CaF2:Tm,Yb@mSiO2 nanofibers and its functionalities, such as drug loading properties, light-triggered drug releasing, optical-monitored drug releasing and light-responsive anticancer efficacy, is also to be revealed in depth. Such new type of multifunctional LDDS, consisting of NIR-triggered releasing, optical monitoring, high loading capacity and biocompatibility properties, is therefore anticipated to pave the way to the future design of advanced drug delivery platforms and the investigation of personalized theraputic protocols for highly varied tumor patients.

本项目针对植入式局部药物输送体系亟需解决的主动药物释控与给药行为实时监测问题，通过溶胶凝胶与电纺技术，基于以介孔孔腔为微反应器的纳米晶原位生长特性，实现镱铥共掺氟化钙（CaF2:Tm,Yb）纳米晶复合介孔氧化硅纤维药物载体材料的构建，并展开其近红外光释控与药物释放光学监测功能研究。揭示表面活性剂、溶胶物理性质及电纺参数对氧化硅纤维介孔特征的影响规律；阐明CaF2:Tm,Yb纳米晶在氧化硅纤维介孔孔腔中的原位生长机制，探究复合纤维物相与微结构对其光致发光性能的影响规律；建立该复合纤维材料与药物加载、光控药物释放、药物释放光学监测及光响应性抗肿瘤性能的构效关系；从而获得一种兼具近红外光释控、释放光学监测、高载量及生物共容性的局部药物输送载体。本项目的实施将为未来适用于不同肿瘤患者的高效药物传输体系设计、制备以及个性化治疗手段研发奠定实验与理论基础。

针对目前肿瘤治疗领域多药耐药性、肿瘤靶向效率低、治疗效能低下等问题，基于溶胶凝胶与电纺技术，以氧化硅等纤维为基质材料，通过原位生长、表面改性、功能复合等多种途径，合成了用于可控药物传输、肿瘤治疗、肿瘤早期检测等多种功能的上转换发光颗粒复合纳米纤维。通过多型“颗粒+纤维”的分级结构复合纤维的构建，实现了治疗因子的病变组织高量定向输运与高效胞内转运。探明了材料微结构、表面特性、外场刺激等对药物负载量、药物释放、外场响应性抗肿瘤效能的调控规律。为目前药物传递和肿瘤治疗领域提供了兼具高药物载量、可控药物释放、多治疗方式协同的多功能局部药物输送与肿瘤治疗材料。此外，为进一步拓展深化该类复合纤维的研究，项目团队进一步开展了用于复合纤维制备所需的多型响应性纳米颗粒材料研究，先后成功合成了钴-二茂铁金属有机框架材料、FeS@BSA纳米团簇等多种纳米颗粒，并初步实现该系列纳米颗粒材料在光动力治疗、光热治疗、电动力治疗、化学动力治疗、气体增敏治疗等治疗手段中的应用探索。为该类外场响应性纤维基定域治疗体系的发展奠定了良好基础。.在本项目的资助下，项目团队基于以上成果在Advanced Materials, Biomaterials等SCI期刊发表论文35篇，授权国家发明专利3件，培养博士毕业生4名，硕士毕业研究生5名，圆满完成了本项目预定的各项目标和任务。