Inorganic nanoparticle-based contrast agents for molecular imaging.

Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imaging, and also touch on contrast enhancement, surface modification, tissue targeting, clearance and toxicity. As research efforts intensify, contrast agents based on inorganic NPs that are highly sensitive, target-specific and safe to use are expected to enter clinical applications in the near future.

[1]  Pai-Chi Li,et al.  In vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods. , 2008, Optics express.

[2]  Donghoon Lee,et al.  In vivo MRI detection of gliomas by chlorotoxin-conjugated superparamagnetic nanoprobes. , 2008, Small.

[3]  R K Jain,et al.  Openings between defective endothelial cells explain tumor vessel leakiness. , 2000, The American journal of pathology.

[4]  P. Reimer,et al.  Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications , 2003, European Radiology.

[5]  Sanjiv S. Gambhir,et al.  Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature , 2007, Journal of Nuclear Medicine.

[6]  Grace Hu,et al.  Molecular MR imaging of melanoma angiogenesis with ανβ3‐targeted paramagnetic nanoparticles , 2005, Magnetic resonance in medicine.

[7]  Philippe Robert,et al.  Recent advances in iron oxide nanocrystal technology for medical imaging. , 2006, Advanced drug delivery reviews.

[8]  Anna Moore,et al.  In Vivo Targeting of Underglycosylated MUC-1 Tumor Antigen Using a Multimodal Imaging Probe , 2004, Cancer Research.

[9]  Tumor imaging using P866, a high‐relaxivity gadolinium chelate designed for folate receptor targeting , 2008, Magnetic resonance in medicine.

[10]  Zhen Cheng,et al.  Ultrasmall near-infrared non-cadmium quantum dots for in vivo tumor imaging. , 2010, Small.

[11]  P. Choyke,et al.  Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. , 2008, Nanomedicine.

[12]  Xiaoyuan Chen,et al.  Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with 64Cu-DOTA-trastuzumab , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[13]  Mitsuo Komatsu,et al.  Organic reactions on silica in water. , 2009, Chemical reviews.

[14]  Xiaohu Gao,et al.  Plasmonic fluorescent quantum dots. , 2009, Nature nanotechnology.

[15]  Dai Fukumura,et al.  InAs(ZnCdS) quantum dots optimized for biological imaging in the near-infrared. , 2009, Journal of the American Chemical Society.

[16]  Anna Moore,et al.  In vivo imaging of tumor response to therapy using a dual‐modality imaging strategy , 2006, International journal of cancer.

[17]  N. K. Prasad,et al.  Mechanism of cell death induced by magnetic hyperthermia with nanoparticles of γ-MnxFe2–xO3 synthesized by a single step process , 2007 .

[18]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[19]  Yusuf Emre Erdi,et al.  The Use of PET for Radiotherapy , 2007 .

[20]  Kai Chen,et al.  Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  Ralph Weissleder,et al.  Detection of early prostate cancer using a hepsin-targeted imaging agent. , 2008, Cancer research.

[22]  Ji-Ho Park,et al.  Cooperative nanomaterial system to sensitize, target, and treat tumors , 2009, Proceedings of the National Academy of Sciences.

[23]  I. Lucet,et al.  Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. , 1996, Journal of microencapsulation.

[24]  P. Jacobs,et al.  Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[25]  Robert Sinclair,et al.  Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. , 2008, Small.

[26]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[27]  Raoul Kopelman,et al.  Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors , 2006, Clinical Cancer Research.

[28]  S Vajda,et al.  Effect of conformational flexibility and solvation on receptor-ligand binding free energies. , 1994, Biochemistry.

[29]  Jin-Sil Choi,et al.  In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. , 2005, Journal of the American Chemical Society.

[30]  T. Quinn,et al.  111In-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide analogues for melanoma imaging. , 2008, Bioconjugate chemistry.

[31]  Warren C W Chan,et al.  Nanoparticle-mediated cellular response is size-dependent. , 2008, Nature nanotechnology.

[32]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[33]  J. Folkman,et al.  Fighting cancer by attacking its blood supply. , 1996, Scientific American.

[34]  Robert Sinclair,et al.  Real-time intravital imaging of RGD-quantum dot binding to luminal endothelium in mouse tumor neovasculature. , 2008, Nano letters.

[35]  G. Whitesides,et al.  Self-assembled monolayers of thiolates on metals as a form of nanotechnology. , 2005, Chemical reviews.

[36]  Wolfhard Semmler,et al.  Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. , 2007, Cancer research.

[37]  Feng Gao,et al.  In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages. , 2010, ACS nano.

[38]  Sanjiv S Gambhir,et al.  Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. , 2006, Nano letters.

[39]  Thomas A. Klar,et al.  Plasmon emission in photoexcited gold nanoparticles , 2004 .

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

[41]  D. Leslie-Pelecky,et al.  Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. , 2008, Molecular pharmaceutics.

[42]  Shuming Nie,et al.  Semiconductor nanocrystals: structure, properties, and band gap engineering. , 2010, Accounts of chemical research.

[43]  Vladimir P Zharov,et al.  Quantum dots as multimodal photoacoustic and photothermal contrast agents. , 2008, Nano letters.

[44]  Anke M Hövels,et al.  MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study. , 2008, The Lancet. Oncology.

[45]  Vincent M Rotello,et al.  Gold nanoparticles in delivery applications. , 2008, Advanced drug delivery reviews.

[46]  Ralph Weissleder,et al.  Long-circulating iron oxides for MR imaging , 1995 .

[47]  J. Bünzli.  Lanthanide luminescence for biomedical analyses and imaging. , 2010, Chemical reviews.

[48]  Younan Xia,et al.  Bright three-photon luminescence from gold/silver alloyed nanostructures for bioimaging with negligible photothermal toxicity. , 2010, Angewandte Chemie.

[49]  B. Kaufmann.  Ultrasound Molecular Imaging of Cardiovascular Disease , 2010 .

[50]  D. A. Capretto,et al.  Receptor-binding, biodistribution, and metabolism studies of 64Cu-DOTA-cetuximab, a PET-imaging agent for epidermal growth-factor receptor-positive tumors. , 2008, Cancer biotherapy & radiopharmaceuticals.

[51]  May D. Wang,et al.  In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags , 2008, Nature Biotechnology.

[52]  D. Elder,et al.  Integrin Distribution in Malignant Melanoma : Association of the ß 3 Subunit with Tumor Progression 1 , 2006 .

[53]  John T Fourkas,et al.  Highly efficient multiphoton-absorption-induced luminescence from gold nanoparticles. , 2005, Nano letters.

[54]  Jeffrey J. Gray,et al.  The interaction of proteins with solid surfaces. , 2004, Current opinion in structural biology.

[55]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[56]  M. Wendland,et al.  MR imaging of ovarian tumors using folate-receptor-targeted contrast agents , 2008, Pediatric Radiology.

[57]  R. Jain.  Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[58]  Younan Xia,et al.  Measuring the Optical Absorption Cross-sections of Au-Ag Nanocages and Au Nanorods by Photoacoustic Imaging. , 2009, The journal of physical chemistry. C, Nanomaterials and interfaces.

[59]  F. Marshall,et al.  In vivo molecular and cellular imaging with quantum dots. , 2005, Current opinion in biotechnology.

[60]  星野 昭芳,et al.  Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification , 2008 .

[61]  Ralph Weissleder,et al.  Nanoparticle imaging of integrins on tumor cells. , 2006, Neoplasia.

[62]  Shuming Nie,et al.  Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals: dual-function microcarriers for optical encoding and magnetic separation. , 2006, Analytical chemistry.

[63]  Noriaki Ohuchi,et al.  In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice. , 2007, Cancer research.

[64]  D. Elder,et al.  Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. , 1990, Cancer research.

[65]  C. Haynes,et al.  Globular proteins at solid/liquid interfaces , 1994 .

[66]  R. Bellamkonda,et al.  Imaging nanoprobe for prediction of outcome of nanoparticle chemotherapy by using mammography. , 2009, Radiology.

[67]  Nathan Kohler,et al.  Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. , 2002, Biomaterials.

[68]  A. Estrada,et al.  Two-photon-induced photoluminescence imaging of tumors using near-infrared excited gold nanoshells , 2008, 2008 Conference on Lasers and Electro-Optics and 2008 Conference on Quantum Electronics and Laser Science.

[69]  Hui Zhang,et al.  Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. , 2005, Nano letters.

[70]  K. Licha.  Contrast Agents for Optical Imaging , 2002 .

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

[72]  Michael J Sailor,et al.  Systematic surface engineering of magnetic nanoworms for in vivo tumor targeting. , 2009, Small.

[73]  Simon R. Cherry,et al.  PET: Physics, Instrumentation, and Scanners , 2006 .

[74]  Antony K. Chen,et al.  Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging , 2006, Annals of Biomedical Engineering.

[75]  Younan Xia,et al.  Gold nanocages as photothermal transducers for cancer treatment. , 2010, Small.

[76]  Younan Xia,et al.  Gold nanocages covered by smart polymers for controlled release with near-infrared light , 2009, Nature materials.

[77]  E. Beaurepaire,et al.  Functionalized fluorescent oxide nanoparticles: Artificial toxins for sodium channel targeting and imaging at the single-molecule level , 2004 .

[78]  J. Fujimoto,et al.  Optical biopsy and imaging using optical coherence tomography , 1995, Nature Medicine.

[79]  Ron C. Hardman.  A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[80]  Michael J Sailor,et al.  Biomimetic amplification of nanoparticle homing to tumors , 2007, Proceedings of the National Academy of Sciences.

[81]  Xinmai Yang,et al.  Nanoparticles for photoacoustic imaging. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[82]  Michael J Sailor,et al.  Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. , 2009, Cancer research.

[83]  Francis Vocanson,et al.  Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging. , 2008, Journal of the American Chemical Society.

[84]  J F Hainfeld,et al.  Gold nanoparticles: a new X-ray contrast agent. , 2006, The British journal of radiology.

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

[86]  R. Robb.  X-ray computed tomography: from basic principles to applications. , 1982, Annual review of biophysics and bioengineering.

[87]  R K Jain,et al.  Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. , 1995, Cancer research.

[88]  K. Nicolay,et al.  Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis. , 2006, Bioconjugate chemistry.

[89]  Raoul Kopelman,et al.  Targeted gold nanoparticles enable molecular CT imaging of cancer. , 2008, Nano letters.

[90]  Susan Newbigging,et al.  In vivo quantum-dot toxicity assessment. , 2010, Small.

[91]  Shimon Weiss,et al.  Synthesis and Properties of Biocompatible Water-Soluble Silica-Coated CdSe/ZnS Semiconductor Quantum Dots† , 2001 .

[92]  M. Wendland,et al.  MR imaging of antigen-induced arthritis with a new, folate receptor-targeted contrast agent. , 2007, Contrast media & molecular imaging.

[93]  Yun Sun,et al.  Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties. , 2010, Biomaterials.

[94]  Xueding Wang,et al.  Picomolar sensitivity MRI and photoacoustic imaging of cobalt nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[95]  Shelton D Caruthers,et al.  Magnetic resonance molecular imaging with nanoparticles , 2004, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[96]  W. Deen,et al.  Structural determinants of glomerular permeability. , 2001, American journal of physiology. Renal physiology.

[97]  V. Hruby,et al.  Emerging approaches in the molecular design of receptor-selective peptide ligands: conformational, topographical and dynamic considerations. , 1990, The Biochemical journal.

[98]  Michael J. Welch,et al.  In vivo evaluation of (64)Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent. , 2010, Bioconjugate chemistry.

[99]  Naomi J Halas,et al.  Nanoshell-enabled photothermal cancer therapy: impending clinical impact. , 2008, Accounts of chemical research.

[100]  P. Perriat,et al.  Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging. , 2007, Journal of the American Chemical Society.

[101]  Miriam Scadeng,et al.  Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival , 2010, Proceedings of the National Academy of Sciences.

[102]  Younan Xia,et al.  Superparamagnetic Colloids: Controlled Synthesis and Niche Applications , 2007 .

[103]  Younan Xia,et al.  Modifying the Surface Properties of Superparamagnetic Iron Oxide Nanoparticles through A Sol−Gel Approach , 2002 .

[104]  S. Gambhir,et al.  Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging. , 2005, Cancer research.

[105]  Atle Bjørnerud,et al.  Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging , 2004, Cell and Tissue Research.

[106]  K. Fujita.  [Two-photon laser scanning fluorescence microscopy]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[107]  G. Whitesides,et al.  Effect of Surface Wettability on the Adsorption of Proteins and Detergents , 1998 .

[108]  Alaaldin M. Alkilany,et al.  Gold nanoparticles in biology: beyond toxicity to cellular imaging. , 2008, Accounts of chemical research.

[109]  Dong Liang,et al.  Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. , 2009, Biomaterials.

[110]  Takuro Niidome,et al.  PEG-modified gold nanorods with a stealth character for in vivo applications. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[111]  W. Bradley,et al.  MRI: The Basics , 1997 .

[112]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[113]  Chenjie Xu,et al.  PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles , 2008, Journal of Nuclear Medicine.

[114]  Elena V. Shevchenko,et al.  Gold/Iron Oxide Core/Hollow‐Shell Nanoparticles , 2008 .

[115]  Younan Xia,et al.  Gold Nanocages: Synthesis, Properties, and Applications , 2009 .

[116]  M. V. van Zandvoort,et al.  Quantitative molecular magnetic resonance imaging of tumor angiogenesis using cNGR-labeled paramagnetic quantum dots. , 2008, Cancer research.

[117]  Sanjiv S. Gambhir,et al.  Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy , 2009, Proceedings of the National Academy of Sciences.

[118]  A. Alivisatos.  Perspectives on the Physical Chemistry of Semiconductor Nanocrystals , 1996 .

[119]  T. Meade,et al.  Magnetic Nanoparticles for Early Detection of Cancer by Magnetic Resonance Imaging , 2009, MRS bulletin.

[120]  J. Willmann,et al.  Imaging of VEGF Receptor in a Rat Myocardial Infarction Model Using PET , 2008, Journal of Nuclear Medicine.

[121]  B. Haraldsson,et al.  A gel-membrane model of glomerular charge and size selectivity in series. , 2001, AJP - Renal Physiology.

[122]  W Semmler,et al.  Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in Vivo by using transferrin receptor pathways , 1998, Magnetic resonance in medicine.

[123]  Tymish Y. Ohulchanskyy,et al.  High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up-conversion in Tm3+ and Yb3+ doped fluoride nanophosphors. , 2008, Nano letters.

[124]  Samuel Achilefu,et al.  Introduction to concepts and strategies for molecular imaging. , 2010, Chemical reviews.

[125]  Jerry S. H. Lee,et al.  Magnetic nanoparticles in MR imaging and drug delivery. , 2008, Advanced drug delivery reviews.

[126]  S. Nie,et al.  Luminescent quantum dots for multiplexed biological detection and imaging. , 2002, Current opinion in biotechnology.