Lledos Marina, Mirabello Vincenzo, Sarpaki Sophia, Ge Haobo, Smugowski Hubert J, Carroll Laurence, Aboagye Eric O, Aigbirhio Franklin I, Botchway Stanley W, Dilworth Jonathan R, Calatayud David G, Plucinski Pawel K, Price Gareth J, Pascu Sofia I
Department of Chemistry University of Bath, Claverton Down BA2 7AY Bath UK.
Department of Surgery and Cancer, Faculty of Medicine, Commonwealth Building, Hammersmith Campus Imperial College London Du Cane Road London W12 0NN UK.
ChemNanoMat. 2018 Apr;4(4):361-372. doi: 10.1002/cnma.201700378. Epub 2018 Feb 8.
Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab-scale, batch-to-batch reproducible copper-64- and gallium-68-radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water-dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes Cu (t=12.7 h) and Ga (t=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC-3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO matrix represents an ideal platform for the incorporation of Cu and Ga radioisotopes with high radiolabelling incorporation.
分子成像已成为临床前和临床研究中用于多种疾病诊断的强大技术。在这项工作中,我们解决了在实现用于细胞成像目的的实验室规模、批次间可重现的铜 - 64和镓 - 68放射性标记金属纳米颗粒(MNP)方面的合成挑战。将包含磁性氧化铁核与发光量子点的复合纳米颗粒同时封装在薄二氧化硅壳内,得到水分散性、生物相容性和发光的纳米颗粒。报道了可扩展的表面修饰方案,以高产率连接放射性同位素铜(半衰期t = 12.7小时)和镓(半衰期t = 68分钟),并且与放射性标记的时间框架兼容。共聚焦和荧光寿命成像研究证实了封装的成像剂在前列腺癌(PC - 3)细胞中的摄取及其在细胞质中的定位。细胞活力测定表明,当荧光团封装在二氧化硅壳内时,系统的生物相容性得到改善。功能性和生物相容性的SiO基质是用于掺入具有高放射性标记掺入率的铜和镓放射性同位素的理想平台。