Applications for site-directed molecular imaging agents coupled with drug delivery potential

Molecular imaging allows non-invasive characterization and quantification of biological processes at cellular and molecular level. Such technologies make it possible to enhance our understanding of drug activity and pharmokinetic properties, and therefore aid decisions to select candidates that are most likely to benefit from targeted drug therapy. Targeted DDSs are nanometer-sized carrier materials designed for improving the biodistribution of systemically applied (chemo-)therapeutics by strictly localizing its pharmacological activity to the site or organ of action. The parallel development of molecular imaging and targeted drug delivery offers great challenges and opportunities for a single multifunctional platform technology, combining targeted motif, therapeutic agents and imaging agents for imaging guided drug delivery. This review article summarizes the synthesis and characterization of various biomaterials that carry targeting motifs, imaging tags and therapeutic agents as theragnostics.

[1]  Robert Langer,et al.  Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. , 2007, Nano letters.

[2]  Vladimir P Torchilin,et al.  PEG-based micelles as carriers of contrast agents for different imaging modalities. , 2002, Advanced drug delivery reviews.

[3]  Sangjin Park,et al.  Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. , 2008, Angewandte Chemie.

[4]  Joe Barfett,et al.  Encapsulated calcium carbonate suspensions: A drug delivery vehicle sensitive to ultrasound disruption , 2006, McGill journal of medicine : MJM : an international forum for the advancement of medical sciences by students.

[5]  Jonathan R. Lindner,et al.  Imaging Tumor Angiogenesis With Contrast Ultrasound and Microbubbles Targeted to &agr;v&bgr;3 , 2003 .

[6]  James F Rusling,et al.  Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. , 2009, ACS nano.

[7]  Britton Chance,et al.  A novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy. , 2005, Bioconjugate chemistry.

[8]  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.

[9]  M. Prato,et al.  Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Sinusas,et al.  Detection of Injury-Induced Vascular Remodeling by Targeting Activated &agr;vβ3 Integrin In Vivo , 2004 .

[11]  T. Iwasaka,et al.  Hepatocyte Growth Factor Delivered by Ultrasound‐Mediated Destruction of Microbubbles Induces Proliferation of Cardiomyocytes and Amelioration of Left Ventricular Contractile Function in Doxorubicin‐Induced Cardiomyopathy , 2005, Stem cells.

[12]  S. Robinson,et al.  90Y and 111In complexes of a DOTA-conjugated integrin alpha v beta 3 receptor antagonist: different but biologically equivalent. , 2004, Bioconjugate chemistry.

[13]  I. Kanno,et al.  Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality. , 2006, Analytical chemistry.

[14]  M S Patterson,et al.  Quantification of bioluminescence images of point source objects using diffusion theory models , 2006, Physics in medicine and biology.

[15]  Klaas Nicolay,et al.  Annexin A5-conjugated quantum dots with a paramagnetic lipidic coating for the multimodal detection of apoptotic cells. , 2006, Bioconjugate chemistry.

[16]  H. Vogel,et al.  In vivo near-infrared fluorescence imaging of integrin alphavbeta3 in an orthotopic glioblastoma model. , 2006, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

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

[18]  Xiaohu Gao,et al.  Quantum dot-amphipol nanocomplex for intracellular delivery and real-time imaging of siRNA. , 2008, ACS nano.

[19]  H. Dai,et al.  Carbon nanotubes as intracellular protein transporters: generality and biological functionality. , 2005, Journal of the American Chemical Society.

[20]  R. Weissleder.  Molecular Imaging in Cancer , 2006, Science.

[21]  T C Skalak,et al.  Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound. , 1998, Circulation.

[22]  Katherine W Ferrara,et al.  Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering , 2009, Physics in medicine and biology.

[23]  E Glenn Tickner,et al.  Characterization of the in vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion molecules. , 2006, Contrast media & molecular imaging.

[24]  M. Dewhirst,et al.  A Tracer Dose of Technetium-99m–Labeled Liposomes Can Estimate the Effect of Hyperthermia on Intratumoral Doxil Extravasation , 2006, Clinical Cancer Research.

[25]  Klaas Nicolay,et al.  Magnetic and fluorescent nanoparticles for multimodality imaging. , 2007, Nanomedicine.

[26]  Christophe Danelon,et al.  Multifunctional lipid/quantum dot hybrid nanocontainers for controlled targeting of live cells. , 2006, Angewandte Chemie.

[27]  N. Quenville,et al.  Photodynamic therapy of squamous cell carcinoma. An evaluation of a new photosensitizing agent, benzoporphyrin derivative and new photoimmunoconjugate. , 1993, Surgical oncology.

[28]  D. Magana,et al.  Switching-on superparamagnetism in Mn/CdSe quantum dots. , 2006, Journal of the American Chemical Society.

[29]  H. Dai,et al.  In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. , 2020, Nature nanotechnology.

[30]  W. Cai,et al.  Multimodality Imaging of IL-18–Binding Protein-Fc Therapy of Experimental Lung Metastasis , 2008, Clinical Cancer Research.

[31]  Hisataka Kobayashi,et al.  Dendrimer-based nanosized MRI contrast agents. , 2004, Current pharmaceutical biotechnology.

[32]  A. Sinusas,et al.  Detection of injury-induced vascular remodeling by targeting activated alphavbeta3 integrin in vivo. , 2004, Circulation.

[33]  Jinwoo Cheon,et al.  A hybrid nanoparticle probe for dual-modality positron emission tomography and magnetic resonance imaging. , 2008, Angewandte Chemie.

[34]  U. Haberkorn.  PET and SPECT. , 2008, Handbook of experimental pharmacology.

[35]  Y. Cohen,et al.  Triggered release of aqueous content from liposome-derived sol-gel nanocapsules. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[36]  R. Sachleben,et al.  Radiolabeled divalent peptidomimetic vitronectin receptor antagonists as potential tumor radiotherapeutic and imaging agents. , 2007, Bioconjugate chemistry.

[37]  P. Cullis,et al.  Tunable pH-sensitive liposomes. , 2004, Methods in enzymology.

[38]  Hui Li,et al.  Peptide-based pharmacomodulation of a cancer-targeted optical imaging and photodynamic therapy agent. , 2007, Bioconjugate chemistry.

[39]  M. Dewhirst,et al.  In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: Illustration of targeted delivery , 2004, Magnetic resonance in medicine.

[40]  M. Brechbiel,et al.  Imaging Acute Renal Failure with Polyamine Dendrimer-Based MRI Contrast Agents , 2006, Nephron Clinical Practice.

[41]  T. Minko,et al.  Receptor targeted polymers, dendrimers, liposomes: which nanocarrier is the most efficient for tumor-specific treatment and imaging? , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[42]  Saed Mirzadeh,et al.  The fate of MAb-targeted Cd(125m)Te/ZnS nanoparticles in vivo. , 2008, Nuclear medicine and biology.

[43]  A. Kassner,et al.  Molecular Imaging of Angiogenesis in Nascent Vx-2 Rabbit Tumors Using a Novel ανβ3-targeted Nanoparticle and 1.5 Tesla Magnetic Resonance Imaging , 2003 .

[44]  Kevin C Weng,et al.  Targeted tumor cell internalization and imaging of multifunctional quantum dot-conjugated immunoliposomes in vitro and in vivo. , 2008, Nano letters.

[45]  J. Jaiswal,et al.  Potentials and pitfalls of fluorescent quantum dots for biological imaging. , 2004, Trends in cell biology.

[46]  Gang Zheng,et al.  Killer beacons for combined cancer imaging and therapy. , 2007, Current medicinal chemistry.

[47]  Michael Reinhardt,et al.  Evaluation of gas-filled microparticles and sonoporation as gene delivery system: feasibility study in rodent tumor models. , 2005, Radiology.

[48]  Klaus Ley,et al.  Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[49]  Sanjiv S Gambhir,et al.  Self-illuminating quantum dot conjugates for in vivo imaging , 2006, Nature Biotechnology.

[50]  V. Fuster,et al.  Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. , 1996, Circulation.

[51]  Kostas Kostarelos,et al.  Functionalized-quantum-dot-liposome hybrids as multimodal nanoparticles for cancer. , 2008, Small.

[52]  Shelton D Caruthers,et al.  Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. , 2003, Cancer research.

[53]  M Schwaiger,et al.  Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[54]  H. Dai,et al.  Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[55]  Sanjiv S Gambhir,et al.  Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic micro-PET in mice. , 2008, Radiology.

[56]  M. Prato,et al.  Translocation of bioactive peptides across cell membranes by carbon nanotubes. , 2004, Chemical communications.

[57]  C. Schell,et al.  Synthesis and investigation of glycosylated mono- and diarylporphyrins for photodynamic therapy. , 1999, Bioorganic & medicinal chemistry.

[58]  S. Wickline,et al.  Time-evolution of enhanced ultrasonic reflection using a fibrin-targeted nanoparticulate contrast agent , 2000, 2000 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.00CH37121).

[59]  Yun Chi,et al.  Iridium-complex-functionalized Fe3O4/SiO2 core/shell nanoparticles: a facile three-in-one system in magnetic resonance imaging, luminescence imaging, and photodynamic therapy. , 2008, Small.

[60]  E. W. Meijer,et al.  Dendritic PARACEST contrast agents for magnetic resonance imaging. , 2007, Contrast media & molecular imaging.

[61]  D. Dione,et al.  Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. , 2004, The Journal of clinical investigation.

[62]  D. Christensen,et al.  Release of doxorubicin from unstabilized and stabilized micelles under the action of ultrasound. , 2007, Journal of nanoscience and nanotechnology.

[63]  S. Bachilo,et al.  Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. , 2004, Journal of the American Chemical Society.

[64]  Sangeeta N. Bhatia,et al.  The European charter for counteracting obesity: A late but important step towards action. Observations on the WHO-Europe ministerial conference, Istanbul, November 15–17, 2006 , 2007, The international journal of behavioral nutrition and physical activity.

[65]  T. Albrecht,et al.  Sonografische Leberdiagnostik bei Tumorpatienten ohne und mit Kontrastmittel , 2008 .

[66]  Christopher H Contag,et al.  In vivo pathology: seeing with molecular specificity and cellular resolution in the living body. , 2007, Annual review of pathology.

[67]  C. Hoeffel,et al.  [Contrast-enhanced ultrasound and liver imaging: review of the literature]. , 2009, Journal de radiologie.

[68]  Shan Jiang,et al.  Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. , 2007, Biomaterials.

[69]  J D Thomas,et al.  Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration. , 2000, Journal of the American College of Cardiology.

[70]  Ralph Weissleder,et al.  Human breast cancer tumor models: molecular imaging of drug susceptibility and dosing during HER2/neu-targeted therapy. , 2008, Radiology.

[71]  H. Mattoussi,et al.  Use of quantum dots for live cell imaging , 2004, Nature Methods.

[72]  T. Webb,et al.  Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[73]  N. Gu,et al.  A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation , 2008, Physics in medicine and biology.

[74]  Joseph Kost,et al.  Smart polymers for responsive drug-delivery systems , 2008, Journal of biomaterials science. Polymer edition.

[75]  S A Wickline,et al.  Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques , 2001, Circulation.

[76]  H. Vogel,et al.  In Vivo Near-Infrared Fluorescence Imaging of Integrin αvβ3 in an Orthotopic Glioblastoma Model , 2006, Molecular Imaging and Biology.

[77]  K. Leong,et al.  Polyethylenimine-grafted multiwalled carbon nanotubes for secure noncovalent immobilization and efficient delivery of DNA. , 2005, Angewandte Chemie.

[78]  W. Cai,et al.  Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein , 2008, Molecular Cancer Therapeutics.

[79]  Stephen Hanessian,et al.  Synthesis of chemically functionalized superparamagnetic nanoparticles as delivery vectors for chemotherapeutic drugs. , 2008, Bioorganic & medicinal chemistry.

[80]  R. Weissleder,et al.  Human myeloperoxidase: A potential target for molecular MR imaging in atherosclerosis , 2004, Magnetic resonance in medicine.

[81]  M. Suematsu,et al.  Mechanism of Hepatic Parenchyma-Specific Contrast of Microbubble-Based Contrast Agent for Ultrasonography: Microscopic Studies in Rat Liver , 2007, Investigative Radiology.

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

[83]  Jiri Sklenar,et al.  Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. , 2003, Circulation.

[84]  M. Schwaiger,et al.  Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[85]  Hua Ai,et al.  Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. , 2006, Nano letters.

[86]  Raffi Bekeredjian,et al.  Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[87]  M. Bruchez,et al.  Turning all the lights on: quantum dots in cellular assays. , 2005, Current opinion in chemical biology.

[88]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[89]  Hugo A Katus,et al.  Ultrasound targeted microbubble destruction for drug and gene delivery. , 2008, Expert opinion on drug delivery.

[90]  Y. Ishida,et al.  Contrast-enhanced intraoperative ultrasonography equipped with late Kupffer-phase image obtained by sonazoid in patients with colorectal liver metastases. , 2008, World journal of gastroenterology.

[91]  H. Oppelaar,et al.  Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy. , 1999, Cancer research.

[92]  P. McCarron,et al.  Photosensitiser delivery for photodynamic therapy. Part 1: Topical carrier platforms. , 2008, Expert opinion on drug delivery.

[93]  Klaas Nicolay,et al.  Lipid‐based nanoparticles for contrast‐enhanced MRI and molecular imaging , 2006, NMR in biomedicine.

[94]  F. Rossi,et al.  Use of contrast-enhanced ultrasound for characterization of focal splenic lesions. , 2008, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[95]  R. Tsien,et al.  The Fluorescent Toolbox for Assessing Protein Location and Function , 2006, Science.

[96]  Sang Cheon Lee,et al.  Fluorescent magnetic nanohybrids as multimodal imaging agents for human epithelial cancer detection. , 2008, Biomaterials.

[97]  Jonathan R. Lindner,et al.  Microbubbles in medical imaging: current applications and future directions , 2004, Nature Reviews Drug Discovery.

[98]  N. Neamati,et al.  Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide–paclitaxel conjugate in mice with breast cancer , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[99]  W. Cai,et al.  In vitro and in vivo characterization of 64Cu-labeled Abegrin, a humanized monoclonal antibody against integrin alpha v beta 3. , 2006, Cancer research.

[100]  D. McPherson,et al.  A method to co-encapsulate gas and drugs in liposomes for ultrasound-controlled drug delivery. , 2008, Ultrasound in medicine & biology.

[101]  S A Wickline,et al.  Molecular imaging of stretch-induced tissue factor expression in carotid arteries with intravascular ultrasound. , 2000, Investigative radiology.

[102]  S. Caruthers,et al.  Imaging of Vx-2 rabbit tumors with alpha(nu)beta3-integrin-targeted 111In nanoparticles. , 2007, International journal of cancer.

[103]  Horst Kessler,et al.  Radiolabeled αvβ3 Integrin Antagonists: A New Class of Tracers for Tumor Targeting , 1999 .

[104]  S S Segal,et al.  The behavior of sonicated albumin microbubbles within the microcirculation: a basis for their use during myocardial contrast echocardiography. , 1989, Circulation research.

[105]  Garry E. Kiefer,et al.  Imaging of Vx‐2 rabbit tumors with ανβ3‐integrin‐targeted 111In nanoparticles , 2007 .

[106]  Stasia A. Anderson,et al.  Magnetic resonance contrast enhancement of neovasculature with αvβ3‐targeted nanoparticles , 2000 .

[107]  Yong Zhang,et al.  Nanoparticles in photodynamic therapy: an emerging paradigm. , 2008, Advanced drug delivery reviews.

[108]  John J. Rossi,et al.  Strategies for silencing human disease using RNA interference , 2007, Nature Reviews Genetics.

[109]  I. Kanno,et al.  Multimodal silica-shelled quantum dots: direct intracellular delivery, photosensitization, toxic, and microcirculation effects. , 2008, Bioconjugate chemistry.

[110]  Chun Yuan,et al.  Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo , 1995, Nature Medicine.

[111]  Kerry K. Karukstis,et al.  Targeted Antiproliferative Drug Delivery to Vascular Smooth Muscle Cells With a Magnetic Resonance Imaging Nanoparticle Contrast Agent: Implications for Rational Therapy of Restenosis , 2002, Circulation.

[112]  P. Cullis,et al.  Tunable pH-sensitive liposomes composed of mixtures of cationic and anionic lipids. , 2000, Biophysical journal.

[113]  Sanjiv S Gambhir,et al.  microPET-Based Biodistribution of Quantum Dots in Living Mice , 2007, Journal of Nuclear Medicine.

[114]  M. Prato,et al.  Applications of carbon nanotubes in drug delivery. , 2005, Current opinion in chemical biology.

[115]  T. Porter,et al.  Myocardial Contrast Echocardiography: A New Gold Standard for Perfusion Imaging? , 2001, Echocardiography.

[116]  Shelton D Caruthers,et al.  Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. , 2003, Circulation.

[117]  R. Duncan.  The dawning era of polymer therapeutics , 2003, Nature Reviews Drug Discovery.

[118]  A R Jayaweera,et al.  Albumin microbubble persistence during myocardial contrast echocardiography is associated with microvascular endothelial glycocalyx damage. , 1998, Circulation.

[119]  Klaas Nicolay,et al.  Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. , 2006, Nano letters.

[120]  Samuel A. Wickline,et al.  Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With &agr;v&bgr;3-Integrin–Targeted Nanoparticles , 2003 .

[121]  O. Wolfbeis,et al.  Dual fluorescence sensor for trace oxygen and temperature with unmatched range and sensitivity. , 2008, Analytical chemistry.

[122]  Jinwoo Cheon,et al.  Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma. , 2006, Angewandte Chemie.

[123]  Zhuang Liu,et al.  Selective probing and imaging of cells with single walled carbon nanotubes as near-infrared fluorescent molecules. , 2008, Nano letters.

[124]  S. Caruthers,et al.  High Sensitivity: High-Resolution SPECT-CT/MR Molecular Imaging of Angiogenesis in the Vx2 Model , 2009, Investigative radiology.

[125]  Noriaki Ohuchi,et al.  In vivo single molecular imaging and sentinel node navigation by nanotechnology for molecular targeting drug-delivery systems and tailor-made medicine , 2008, Breast cancer.

[126]  Sanjiv S Gambhir,et al.  Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. , 2008, Radiology.

[127]  D. Miller,et al.  Diagnostic Ultrasound Activation of Contrast Agent Gas Bodies Induces Capillary Rupture in Mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[128]  Ganesh D. Sockalingum,et al.  Intracellular Applications of Analytical SERS Spectroscopy and Multispectral Imaging , 2008 .

[129]  Shuming Nie,et al.  Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging. , 2008, Journal of the American Chemical Society.

[130]  Zhuang Liu,et al.  Drug delivery with carbon nanotubes for in vivo cancer treatment. , 2008, Cancer research.

[131]  Donghoon Lee,et al.  Optical and MRI multifunctional nanoprobe for targeting gliomas. , 2005, Nano letters.

[132]  Andrej Lyshchik,et al.  Relationship Between Retention of a Vascular Endothelial Growth Factor Receptor 2 (VEGFR2)‐Targeted Ultrasonographic Contrast Agent and the Level of VEGFR2 Expression in an In Vivo Breast Cancer Model , 2008, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[133]  S. Gambhir,et al.  Noninvasive molecular imaging of small living subjects using Raman spectroscopy , 2008, Proceedings of the National Academy of Sciences.

[134]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[135]  J. G. Miller,et al.  A novel site-targeted ultrasonic contrast agent with broad biomedical application. , 1996, Circulation.

[136]  Ralph Weissleder,et al.  A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. , 2003, Cancer research.

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

[138]  S A Wickline,et al.  Magnetic resonance contrast enhancement of neovasculature with alpha(v)beta(3)-targeted nanoparticles. , 2000, Magnetic resonance in medicine.

[139]  U. Schmidt-Erfurth,et al.  Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates. , 1997, British Journal of Cancer.

[140]  Xiaoyuan Chen,et al.  Intracellular delivery of an anionic antisense oligonucleotide via receptor-mediated endocytosis , 2008, Nucleic acids research.

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

[142]  W. Pitt,et al.  A polymeric micelle system with a hydrolysable segment for drug delivery , 2006, Journal of biomaterials science. Polymer edition.

[143]  J. G. Miller,et al.  In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy. , 1998, The Journal of the Acoustical Society of America.

[144]  B. Wilson,et al.  Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation , 2007, Proceedings of the National Academy of Sciences.

[145]  Erkki Ruoslahti,et al.  Targeted quantum dot conjugates for siRNA delivery. , 2007, Bioconjugate chemistry.

[146]  Kai Chen,et al.  Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[147]  Zhuang Liu,et al.  Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. , 2005, Journal of the American Chemical Society.

[148]  P. Carter,et al.  Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies , 1993, Cancer Immunology, Immunotherapy.

[149]  M. Bednarski,et al.  Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. , 1998, Nature medicine.

[150]  Wolfhard Semmler,et al.  Vessel fractions in tumor xenografts depicted by flow- or contrast-sensitive three-dimensional high-frequency Doppler ultrasound respond differently to antiangiogenic treatment. , 2008, Cancer research.

[151]  Y. Negishi,et al.  Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

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

[153]  B. Wang,et al.  Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo , 2008, Thrombosis and Haemostasis.

[154]  H. Maeda,et al.  Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. , 1992, Bioconjugate chemistry.

[155]  Steven A Curley,et al.  Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence , 2006, Proceedings of the National Academy of Sciences.

[156]  David D McPherson,et al.  Fibrin targeting of echogenic liposomes with inactivated tissue plasminogen activator. , 2008, Journal of liposome research.

[157]  H. Dai,et al.  Soluble single-walled carbon nanotubes as longboat delivery systems for platinum(IV) anticancer drug design. , 2007, Journal of the American Chemical Society.

[158]  W. Cai,et al.  In vitro and In vivo Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin αvβ3 , 2006 .

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

[160]  Tsukasa Akasaka,et al.  Biological behavior of hat-stacked carbon nanofibers in the subcutaneous tissue in rats. , 2005, Nano letters.

[161]  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.

[162]  H. Oppelaar,et al.  Targeting of aluminum (III) phthalocyanine tetrasulfonate by use of internalizing monoclonal antibodies: improved efficacy in photodynamic therapy. , 2001, Cancer research.

[163]  P. Choyke,et al.  Design, synthesis, and characterization of a dual modality positron emission tomography and fluorescence imaging agent for monoclonal antibody tumor-targeted imaging. , 2007, Journal of medicinal chemistry.

[164]  P. Baron,et al.  Exposure to Carbon Nanotube Material: Aerosol Release During the Handling of Unrefined Single-Walled Carbon Nanotube Material , 2004, Journal of toxicology and environmental health. Part A.