State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610000, P. R. China.
J Mater Chem B. 2020 Mar 11;8(10):2107-2114. doi: 10.1039/c9tb02787d.
In recent years, nano-hydroxyapatite (nHAp) based dual-/multi-modal bioimaging systems have received significant attention due to their excellent bioactivity and biocompatibility. Specifically, co-doping two or more ions (such as Eu3+, Te3+, Gd3+ and Mn2+) into the lattice of nHAp can directly endow nHAp with multimodal imaging properties. However, the main strategy for the construction of co-doped nHAp nanocrystals depends on high temperature and techniques of post-modification, which could lead to inevitable nHAp crystal polymerization and increased particle size. Thus, the complexity of the preparation could further limit the clinical applications. Herein, based on the specific binding between hyaluronan and CD44 protein, a biomimetic synthesis method using hyaluronan as a template was explored for the construction of Eu/Ba co-doped and F-substituted nHAp (HA@nFAp:Eu/Ba) with recognition capability. The as-prepared HA@nFAp:Eu/Ba nanocrystals possessed uniform and spindle-like morphology with good monodispersity. Compared with co-doped nFAp that was synthesized under hyaluronan-free and high-temperature hydrothermal conditions, this one-step synthesized HA@nFAp:Eu/Ba presented improved doping efficiency and colloidal stability, realizing high sensitivity in both CT and fluorescence imaging. Besides, cytotoxicity studies indicated that the developed HA@nFAp:Eu/Ba nanocrystals exhibited good compatibility in both cells and mice. Meanwhile, the HA@nFAp:Eu/Ba nanocrystals also demonstrated tumor targeted stability in both cancer cells and living mice according to the favourable results from CT and fluorescence imaging. Therefore, this biomimetic synthesis strategy allowed multi-functionalization of nHAp in one pot under mild conditions.
近年来，基于纳米羟基磷灰石（nHAp）的双模态/多模态生物成像系统因其优异的生物活性和生物相容性而受到广泛关注。具体而言，将两种或多种离子（如 Eu3+、Te3+、Gd3+和 Mn2+）共掺杂到 nHAp 的晶格中可以直接赋予 nHAp 多模态成像特性。然而，共掺杂 nHAp 纳米晶的主要构建策略依赖于高温和后修饰技术，这可能导致不可避免的 nHAp 晶体聚合和粒径增加。因此，制备的复杂性可能会进一步限制其临床应用。在此，基于透明质酸（HA）与 CD44 蛋白之间的特异性结合，探索了一种使用 HA 作为模板的仿生合成方法，用于构建具有识别能力的 Eu/Ba 共掺杂和 F 取代的 nHAp（HA@nFAp:Eu/Ba）。所制备的 HA@nFAp:Eu/Ba 纳米晶具有均匀的纺锤形形貌和良好的单分散性。与在无 HA 和高温水热条件下合成的共掺杂 nFAp 相比，一步法合成的 HA@nFAp:Eu/Ba 具有更高的掺杂效率和胶体稳定性，在 CT 和荧光成像中均实现了高灵敏度。此外，细胞毒性研究表明，所开发的 HA@nFAp:Eu/Ba 纳米晶在细胞和小鼠中均表现出良好的相容性。同时，根据 CT 和荧光成像的良好结果，HA@nFAp:Eu/Ba 纳米晶在癌细胞和活体小鼠中也表现出肿瘤靶向稳定性。因此，这种仿生合成策略允许在温和条件下一锅法实现 nHAp 的多功能化。
