Synthesis of biocompatible and magnetic fluorescent nanodiamonds for cell manipulation and imaging

[[abstract]]製備多功能性的奈米粒子是目前材料科學界的一項具挑戰性的目標，經由不同材料的性質搭配，使其組合後可以應用的範圍更具多樣性，包括藥物傳遞，癌症診斷及治療，表面性質的改變和生物成像等。其中由於化學穩定性佳，良好的生物相容性，表面易於官能化，並且生物毒性低，奈米鑽石非常適合成為多功能奈米粒子的材料之一。 在本篇論文中，我們開發出一種簡單的方式合成出兼具螢光、磁性和良好生物相容性性質的複合性奈米粒子。透過使用螢光奈米鑽石做為基本核心載體，將聚精胺酸與鑽石上之羧酸官能基以共價鍵結合，而聚精胺酸其上帶正電性胍基團以物理吸附的方式吸附帶負電性的四氧化三鐵奈米粒子與肝素多醣。合成得到之複合性奈米粒子的大小尺度約為160 nm，飽和磁化強度為4.35 emu/g，同時可吸收532 nm附近光源而放出波長大於600 nm的紅色螢光，及非常低的細胞毒性。四氧化三鐵的量為64 μg於1 mg的鑽石載體上，而在奈米鑽石上之肝素多醣的量約為24.4 μg 。 本篇論文證明此種複合性奈米粒子在標記體外HeLa細胞的實驗上，與螢光奈米鑽石同樣皆以胞吞作用的機制進入細胞，停留於細胞質中。而在進入細胞後並不會改變細胞的大小，細胞餵食的濃度在100 μg/mL趨近於飽和。另外可使用外加磁場調控已標記此奈米粒子的細胞。 而在未來的研究上，此複合性奈米粒子可以在體內成像的領域上提供細胞螢光標記及核磁共振攝影（MRI）以及用磁場調控細胞移動的應用。[[abstract]]Recent advances in nanotechnology for biomedical applications have rapidly growing needs for developing multifunctional nanoparticles. Here, one new class of fluorescent nanodiamond(FND) hybrids that process biocompatible, fluorescent and magnetic functionalities is presented. Magnetic iron oxide/Fluorescent nanodiamond (IO/FND) hybrids are prepared from 100 nm FNDs functionalized at the surface with polyarginine brushes to accommodate the 20 nm magnetic IOs, and then coating with a biocompatible Heparin layer. These new FND hybrids exhibit both fluorescent and magnetic properties with a maximum saturation magnetization of 4.35 emu g-1 and far-red fluorescence emission. The fluorescent intensity of FND hybrids is similar to bare FND. MTS assay reveals that FND Hybrids show have extremely low cytotoxicity toward HeLa cells. The FND hybrids are demonstrated with HeLa cell line for in vitro cellular labeling/imaging and magnetic cell manipulation. The fluorescence intensities were increased in a concentration-dependent manner by treatment with FND hybrids in HeLa cells. However, the existence of FND hybrids inside the cells did not alter cellular size distribution. The approach should be widely applicable to incorporate into a variety of biomedical applications such as hyperthermia, long-term magnetic resonance and fluorescence imaging, cell manipulation and separation.[[note]]碩