In vivo cancer targeting and imaging with semiconductor quantum dots

We describe the development of multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) for cancer targeting and imaging in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer and linking this amphiphilic polymer to tumor-targeting ligands and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mice indicate that the QD probes accumulate at tumors both by the enhanced permeability and retention of tumor sites and by antibody binding to cancer-specific cell surface biomarkers. Using both subcutaneous injection of QD-tagged cancer cells and systemic injection of multifunctional QD probes, we have achieved sensitive and multicolor fluorescence imaging of cancer cells under in vivo conditions. We have also integrated a whole-body macro-illumination system with wavelength-resolved spectral imaging for efficient background removal and precise delineation of weak spectral signatures. These results raise new possibilities for ultrasensitive and multiplexed imaging of molecular targets in vivo.

[1]  A. Welch,et al.  A review of the optical properties of biological tissues , 1990 .

[2]  C. Wang,et al.  Improved gene expression by a modified bicistronic retroviral vector. , 1995, Biochemical and biophysical research communications.

[3]  A. Alivisatos Semiconductor Clusters, Nanocrystals, and Quantum Dots , 1996, Science.

[4]  M. Nirmal,et al.  Fluorescence intermittency in single cadmium selenide nanocrystals , 1996, Nature.

[5]  John W. Park,et al.  Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human breast cancer cells in vitro. , 1997, Biochemistry.

[6]  M. Bawendi,et al.  Quantum-confined stark effect in single CdSe nanocrystallite quantum dots , 1997, Science.

[7]  D. Balding,et al.  HLA Sequence Polymorphism and the Origin of Humans , 2006 .

[8]  S. Nie,et al.  Quantum dot bioconjugates for ultrasensitive nonisotopic detection. , 1998, Science.

[9]  George M Whitesides,et al.  Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors. , 1998, Angewandte Chemie.

[10]  Christine Allen,et al.  Nano-engineering block copolymer aggregates for drug delivery , 1999 .

[11]  R. Steinman,et al.  Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. , 1999, Immunity.

[12]  R K Jain,et al.  Transport of molecules, particles, and cells in solid tumors. , 1999, Annual review of biomedical engineering.

[13]  Ralph Weissleder,et al.  Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells , 2000, Nature Biotechnology.

[14]  J. Matthew Mauro,et al.  Self-Assembly of CdSe−ZnS Quantum Dot Bioconjugates Using an Engineered Recombinant Protein , 2000 .

[15]  C. Evans,et al.  Surface transformation and photoinduced recovery in CdSe nanocrystals. , 2001, Physical review letters.

[16]  V. Reuter,et al.  Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. , 2001, Urology.

[17]  C. Niemeyer REVIEW Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science , 2022 .

[18]  Xiaogang Peng,et al.  Alternative Routes toward High Quality CdSe Nanocrystals , 2001 .

[19]  R K Jain,et al.  Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[20]  S. Nie,et al.  Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules , 2001, Nature Biotechnology.

[21]  Xiaogang Peng,et al.  Formation of high-quality CdTe, CdSe, and CdS nanocrystals using CdO as precursor. , 2001, Journal of the American Chemical Society.

[22]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Ralph Weissleder,et al.  Tat peptide directs enhanced clearance and hepatic permeability of magnetic nanoparticles. , 2002, Bioconjugate chemistry.

[24]  James McBride,et al.  Targeting cell surface receptors with ligand-conjugated nanocrystals. , 2002, Journal of the American Chemical Society.

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

[26]  Vladimir P Torchilin,et al.  Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. , 2002, Cancer research.

[27]  Ralph Weissleder,et al.  Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes. , 2002, Bioconjugate chemistry.

[28]  Meng Yang,et al.  Direct external imaging of nascent cancer, tumor progression, angiogenesis, and metastasis on internal organs in the fluorescent orthotopic model , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[29]  A. P. Alivisatos,et al.  Epitaxial growth and photochemical annealing of graded CdS/ZnS shells on colloidal CdSe nanorods. , 2002, Journal of the American Chemical Society.

[30]  R. Weissleder,et al.  Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging , 2002, European Radiology.

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

[32]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[33]  S. Nie,et al.  Molecular profiling of single cells and tissue specimens with quantum dots. , 2003, Trends in biotechnology.

[34]  D. Maysinger,et al.  Micellar Nanocontainers Distribute to Defined Cytoplasmic Organelles , 2003, Science.

[35]  Shuming Nie,et al.  Doping Mesoporous Materials with Multicolor Quantum Dots , 2003 .

[36]  C. Walle,et al.  Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles , 2003, Nature.

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

[38]  K. Roth,et al.  Combined Tyramide Signal Amplification and Quantum Dots for Sensitive and Photostable Immunofluorescence Detection , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[39]  W. Webb,et al.  Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo , 2003, Science.

[40]  Igor L. Medintz,et al.  Self-assembled nanoscale biosensors based on quantum dot FRET donors , 2003, Nature materials.

[41]  J. Matthew Mauro,et al.  Long-term multiple color imaging of live cells using quantum dot bioconjugates , 2003, Nature Biotechnology.

[42]  S. Ludwigs,et al.  Self-assembly of functional nanostructures from ABC triblock copolymers , 2003, Nature materials.

[43]  Thomas M. Jovin,et al.  Quantum dots finally come of age , 2003, Nature Biotechnology.

[44]  William C. Olson,et al.  The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[45]  George C Schatz,et al.  What controls the melting properties of DNA-linked gold nanoparticle assemblies? , 2000, Journal of the American Chemical Society.

[46]  S. Vallabhajosula,et al.  Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. , 2003, The Journal of urology.

[47]  M. Bawendi,et al.  Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. , 2003, Journal of the American Chemical Society.

[48]  Shuming Nie,et al.  Alloyed semiconductor quantum dots: tuning the optical properties without changing the particle size. , 2003, Journal of the American Chemical Society.

[49]  Yong Taik Lim,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular imaging.

[50]  T. Mihaljevic,et al.  Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping , 2004, Nature Biotechnology.

[51]  J. Post,et al.  Quantum dot ligands provide new insights into erbB/HER receptor–mediated signal transduction , 2004, Nature Biotechnology.

[52]  Byron Ballou,et al.  Noninvasive imaging of quantum dots in mice. , 2004, Bioconjugate chemistry.

[53]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[54]  Shuming Nie,et al.  Quantum dot-encoded mesoporous beads with high brightness and uniformity: rapid readout using flow cytometry. , 2004, Analytical chemistry.

[55]  Richard M. Levenson,et al.  Spectral Imaging and Pathology: Seeing More , 2004 .