Chemical synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications

Magnetic iron oxide nanoparticles have been extensively investigated for their various biomedical applications including diagnostic imaging, biological sensing, drug, cell, and gene delivery, and cell tracking. Recent advances in the designed synthesis and assembly of uniformly sized iron oxide nanoparticles have brought innovation in the field of nanomedicine. This Account provides a review on the recent progresses in the controlled synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications. In particular, it focuses on three topics: stringent control of particle size during synthesis via the "heat-up" process, surface modification for the high stability and biocompatibility of the nanoparticles for diagnostic purposes, and assembly of the nanoparticles within polymers or mesoporous silica matrices for theranostic applications. Using extremely small 3 nm sized iron oxide nanoparticles (ESION), a new nontoxic T1 MRI contrast agent was realized for high-resolution MRI of blood vessels down to 0.2 mm. Ferrimagnetic iron oxide nanoparticles (FION) that are larger than 20 nm exhibit extremely large magnetization and coercivity values. The cells labeled with FIONs showed very high T2 contrast effect so that even a single cell can be readily imaged. Designed assembly of iron oxide nanoparticles with mesoporous silica and polymers was conducted to fabricate multifunctional nanoparticles for theranostic applications. Mesoporous silica nanoparticles are excellent scaffolds for iron oxide nanoparticles, providing magnetic resonance and fluorescence imaging modalities as well as the functionality of the drug delivery vehicle. Polymeric ligands could be designed to respond to various biological stimuli such as pH, temperature, and enzymatic activity. For example, we fabricated tumor pH-sensitive magnetic nanogrenades (termed PMNs) composed of self-assembled iron oxide nanoparticles and pH-responsive ligands. They were utilized to visualize small tumors (<3 mm) via pH-responsive T1 MRI and fluorescence imaging. Also, superior photodynamic therapeutic efficacy in highly drug-resistant heterogeneous tumors was observed. We expect that these multifunctional and bioresponsive nanoplatforms based on uniformly sized iron oxide nanoparticles will provide more unique theranostic approaches in clinical uses.