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.

[1]  Jie Zhou,et al.  Enzymatic Transformation of Phosphate Decorated Magnetic Nanoparticles for Selectively Sorting and Inhibiting Cancer Cells , 2014, Bioconjugate chemistry.

[2]  Taeghwan Hyeon,et al.  pH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma. , 2014, ACS nano.

[3]  T. Hyeon,et al.  Surface ligands in synthesis, modification, assembly and biomedical applications of nanoparticles , 2014 .

[4]  T. Hyeon,et al.  Multi-modal transfection agent based on monodisperse magnetic nanoparticles for stem cell gene delivery and tracking. , 2014, Biomaterials.

[5]  Taeghwan Hyeon,et al.  Multifunctional tumor pH-sensitive self-assembled nanoparticles for bimodal imaging and treatment of resistant heterogeneous tumors. , 2014, Journal of the American Chemical Society.

[6]  T. Hyeon,et al.  Cancer imaging: Lighting up tumours. , 2014, Nature materials.

[7]  Chun Li,et al.  A targeted approach to cancer imaging and therapy. , 2014, Nature materials.

[8]  T. Hyeon,et al.  Chemical design of biocompatible iron oxide nanoparticles for medical applications. , 2013, Small.

[9]  Hua Ai,et al.  Applications and potential toxicity of magnetic iron oxide nanoparticles. , 2013, Small.

[10]  Samuel Woojoo Jun,et al.  Sizing by weighing: characterizing sizes of ultrasmall-sized iron oxide nanocrystals using MALDI-TOF mass spectrometry. , 2013, Journal of the American Chemical Society.

[11]  Patrick Couvreur,et al.  Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. , 2012, Chemical reviews.

[12]  Johannes T. Heverhagen,et al.  Biological Applications of Magnetic Nanoparticles , 2012 .

[13]  Bing Xu,et al.  Magnetic Nanoparticles for the Manipulation of Proteins and Cells , 2012 .

[14]  Taeghwan Hyeon,et al.  Designed Synthesis of Uniformly Sized Iron Oxide Nanoparticles for Efficient Magnetic Resonance Imaging Contrast Agents , 2012 .

[15]  Ronnie H. Fang,et al.  In vivo clearance and toxicity of monodisperse iron oxide nanocrystals. , 2012, ACS nano.

[16]  T. Park,et al.  Chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes for magnetically modulated cancer hyperthermia. , 2012, ACS nano.

[17]  S. Choi,et al.  Water-dispersible ferrimagnetic iron oxide nanocubes with extremely high r₂ relaxivity for highly sensitive in vivo MRI of tumors. , 2012, Nano letters.

[18]  Juan L. Vivero-Escoto,et al.  Silica-based nanoprobes for biomedical imaging and theranostic applications. , 2012, Chemical Society reviews.

[19]  S. Choi,et al.  Multiple-interaction ligands inspired by mussel adhesive protein: synthesis of highly stable and biocompatible nanoparticles. , 2011, Angewandte Chemie.

[20]  Ralph Weissleder,et al.  Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. , 2011, Accounts of chemical research.

[21]  Taeghwan Hyeon,et al.  Multifunctional mesoporous silica nanocomposite nanoparticles for theranostic applications. , 2011, Accounts of chemical research.

[22]  J. Cheon,et al.  Theranostic magnetic nanoparticles. , 2011, Accounts of chemical research.

[23]  Taeghwan Hyeon,et al.  Large-scale synthesis of uniform and extremely small-sized iron oxide nanoparticles for high-resolution T1 magnetic resonance imaging contrast agents. , 2011, Journal of the American Chemical Society.

[24]  Xiaolian Sun,et al.  Monodisperse magnetic nanoparticles for theranostic applications. , 2011, Accounts of chemical research.

[25]  Hua Ai,et al.  Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. , 2011, Accounts of chemical research.

[26]  Taeghwan Hyeon,et al.  Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets , 2011, Proceedings of the National Academy of Sciences.

[27]  Taeghwan Hyeon,et al.  Large-Scale Synthesis of Uniform and Extremely Small-Sized Iron Oxide Nanoparticles for High-Resolution T 1 Magnetic Resonance Imaging Contrast Agents , 2011 .

[28]  Gang Bao,et al.  Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity. , 2010, Nano letters.

[29]  Chad A. Mirkin,et al.  Gold nanoparticles for biology and medicine. , 2010, Angewandte Chemie.

[30]  Miqin Zhang,et al.  Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. , 2010, Advanced drug delivery reviews.

[31]  Taeghwan Hyeon,et al.  Uniform mesoporous dye-doped silica nanoparticles decorated with multiple magnetite nanocrystals for simultaneous enhanced magnetic resonance imaging, fluorescence imaging, and drug delivery. , 2010, Journal of the American Chemical Society.

[32]  E. Kumacheva,et al.  Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. , 2010, Nature nanotechnology.

[33]  Zahi A Fayad,et al.  Iron oxide core oil-in-water emulsions as a multifunctional nanoparticle platform for tumor targeting and imaging. , 2009, Biomaterials.

[34]  Taeghwan Hyeon,et al.  Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. , 2009, Chemical Society reviews.

[35]  Taeghwan Hyeon,et al.  Synthesis of uniform ferrimagnetic magnetite nanocubes. , 2009, Journal of the American Chemical Society.

[36]  Andrew A. Burns,et al.  Inside Front Cover: Designed Fabrication of Silica‐Based Nanostructured Particle Systems for Nanomedicine Applications (Adv. Funct. Mater. 23/2008) , 2008 .

[37]  Taeghwan Hyeon,et al.  Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery. , 2008, Angewandte Chemie.

[38]  C. Robic,et al.  Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. , 2008, Chemical reviews.

[39]  J. Cheon,et al.  Nanoscaling Laws of Magnetic Nanoparticles and Their Applicabilities in Biomedical Sciences , 2008 .

[40]  Jung Ho Yu,et al.  Designed Fabrication of a Multifunctional Polymer Nanomedical Platform for Simultaneous Cancer‐ Targeted Imaging and Magnetically Guided Drug Delivery , 2008 .

[41]  Taeghwan Hyeon,et al.  Versatile PEG-derivatized phosphine oxide ligands for water-dispersible metal oxide nanocrystals. , 2007, Chemical communications.

[42]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[43]  T. Hyeon,et al.  Kinetics of monodisperse iron oxide nanocrystal formation by "heating-up" process. , 2007, Journal of the American Chemical Society.

[44]  Shuming Nie,et al.  Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. , 2007, Journal of the American Chemical Society.

[45]  A. Tanimoto,et al.  Application of superparamagnetic iron oxide to imaging of hepatocellular carcinoma. , 2006, European journal of radiology.

[46]  Jinwoo Cheon,et al.  Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling. , 2005, Journal of the American Chemical Society.

[47]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[48]  T. Hyeon,et al.  One-nanometer-scale size-controlled synthesis of monodisperse magnetic iron oxide nanoparticles. , 2005, Angewandte Chemie.

[49]  Taeghwan Hyeon,et al.  Ultra-large-scale syntheses of monodisperse nanocrystals , 2004, Nature materials.

[50]  William W. Yu,et al.  Synthesis of monodisperse iron oxide nanocrystals by thermal decomposition of iron carboxylate salts. , 2004, Chemical communications.

[51]  Xiaogang Peng,et al.  Size- and Shape-Controlled Magnetic (Cr, Mn, Fe, Co, Ni) Oxide Nanocrystals via a Simple and General Approach , 2004 .

[52]  Bing Xu,et al.  Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles. , 2004, Journal of the American Chemical Society.

[53]  Moungi G Bawendi,et al.  Oligomeric ligands for luminescent and stable nanocrystal quantum dots. , 2003, Journal of the American Chemical Society.

[54]  Vincent Noireaux,et al.  In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles , 2002, Science.

[55]  Hao Zeng,et al.  Size-controlled synthesis of magnetite nanoparticles. , 2002, Journal of the American Chemical Society.

[56]  Taeghwan Hyeon,et al.  Synthesis of highly crystalline and monodisperse maghemite nanocrystallites without a size-selection process. , 2001, Journal of the American Chemical Society.

[57]  G. Palade,et al.  Neovasculature induced by vascular endothelial growth factor is fenestrated. , 1997, Cancer research.

[58]  S. Moghimi.  Mechanisms of splenic clearance of blood cells and particles : towards development of new splenotropic agents , 1995 .

[59]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.