Keywords: Fe3O4, magnetic nanoparticle, drug delivery
Summary:Introduction: The development of magnetic nano-materials has been of great interest over the past decades. Their unique magnetic properties have fascinated many researchers, and the applications of their properties have engaged diverse areas of biomedicine and engineering, including magnetic resonance imaging, drug loading, and targeted delivery, and hyperthermia agents for cancer treatment. To further make their applications more practical and higher performances, enhanced susceptibility of the nanomaterials is desired. Here we report a systematic approach for forming libraries of multicore iron oxide nanoparticles (MIONs) with superior susceptibility, to meet the demand of different optimization of magnetic properties. Results: The MIONs are aggregates of small nanocrystals (primary particles) as shown by TEM. We have synthe-sized a library of multicore iron oxide nanoparticles whose primary particle size and cluster dimension can be independently controlled by the reaction temperature and mass of added water, respectively. Both the cluster size and primary particle size can vary over a wide range. The MIONs are superparamagnetic as indicated by VSM. At low applied magnetic fields on the order of Gauss, the magnetization of the multicore sample is much greater than that of the single-core nanoparticle, suggesting a superior susceptibility. The as-synthesized MIONs, with a cluster size of 25 nm and primary particle size of 4 nm, is very stable in pure water but are prone to aggregation in cell culturing media with high ionic strength and crosslinking agents such as Ca2+. However, after surface modification with PMAO-PEG-Dopa, the MIONs colloidal stability is greatly en-hanced. The introduction of PEG also facilitates the bio-compatibility of the MIONs. The PMAO functionalized MIONs are then labeled by DiI. The color of the DiI labeled MIONs solution is between that of the original MIONs solution and DiI solu-tion, indicating the successful attachment of DiI onto the MIONs. Fluorescence spectra also confirm such observa-tion, as the fluorescent pattern of the DiI labeled MIONs is pretty similar to that of DiI solution, while the original MIONs shows no significant fluorescence. The DiI labeled MIONs are subsequently tested in U2OS cell. The centering blue area is the nucleus of the cancer cell. The green dots are the lysosome while the red dots, distributed within the cell, are the DiI labeled MIONs. The MIONs successfully entering the cell membranes directed by external magnet indicates their promising applications for biomedicines. Conclusions: We have developed a synthetic strategy for forming libraries of biocompatible multicore iron oxide nanoparticles of tunable dimensions. These MIONs could successfully enter the cancer cells after surface modifications and labeling with florescent dye. Our preliminary experimental results shown here are very promising for biomedical applications, and a systematic investigation is underway.