多层金纳米壳复合材料的可控制备及其生物医学性能研究

It has been demonstrated by theoretical study that multilayered gold nanoshells possess excellent photothermal performance due to the unique nanostructure. However, it is very difficult to fabricate with the conventional strategies. In this work, a simple and controllable synthetic route will be developed to obtain monodispersed nanocomposite with a novel "Au@organosilica@Au" nanostructure. These will be achived by the direct self-condensation of organic silanes to form the organosilica interlayer onto Au core and the subsequent "in situ reduction and growth" of Au nanoshell.In the meantime, Raman reporting molecules is introduced into the nanostrucutre, so that a novel kind of nanocomposite with SERS and photothermal performance is fabricated. The controlled synthesis of the organosilica and gold nanoshell will be investigated in detail. The growth mechanism of the gold nanoshell will be proposed. With this newly developed methodology, the problems such as the complicated process, the easy aggregation between the nanoparticles and the unstable photothermal and SERS performance of the resultant nanocomposites will be solved. Moreover, this methodology can be employed to synthesize other multifunctional nanocomposite by choosing different structured nanoparticles as the inner cores.

围绕多层金纳米壳复合结构，针对其理论计算具有优异的光热特性但制备困难的问题，本课题创新地设计了以有机硅烷自缩聚形成的有机硅作为中间层的"金@有机硅@金"纳米复合结构，提出将拉曼报告分子嵌入内核金纳米粒子表面的设计思想，发展一种全新、简单可控的合成策略，得到一类具有优异SERS拉曼成像检测和光热治疗性能的材料。通过研究制备过程中有机硅和金纳米壳层的控制生长、多层金纳米复合结构与其等离子共振和拉曼增强特性之间的关系等基础科学问题，总结出金纳米壳"原位还原－生长"的机理，解决多层金纳米复合结构制备过程复杂、易团聚、光热稳定性差、拉曼信号弱等关键问题，并为理论研究提供相应的实验基础；同时，这一合成策略还可进一步拓展，将内核更换为不同形状的Ag, Fe3O4等纳米颗粒，制备系列多功能复合结构纳米颗粒。可见，本项目的顺利完成具有重要的学术价值和应用前景。

本项目针对传统金基纳米复合材料制备工艺复杂，成本高等问题，率先提出原位生长与多组元调控相耦合策略构筑系列新型多组分复合纳米结构，实现了对模型肿瘤影像导航下的精准治疗，揭示了杂化材料结构与成像和治疗性能稳定性之间的关系，为金基杂化纳米颗粒用于生物医学领域提供理论基础。其中，标志性的成果主要包括：1）采用有机硅烷形成的有机硅球为模板，通过原位类Brust还原“种子”生长法制备具有形貌可控、粒径可调以及单分散特点的金纳米壳；2）采用有机硅为中间介电层，以原位还原、类 Brust 反应和有机硅直接包覆工作为基础，发展简单、高效的合成方法制备得到 Au@有机硅@Au 多层金纳米壳用于SERS成像测引导下的肿瘤光热治疗研究；3）以有机硅直接包覆金纳米星颗粒为基础，简单、高效地制备出一类具有近红外光吸收能力、SERS 能力和增强 T1 造影能力的金纳米星复合材料。在本项目的资助下，在Biomaterials, Small, Langmuir等期刊发表论文20篇，培养博士研究生3名、硕士研究生2名。