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Quantum Dots and Targeted Nanoparticle Probes for In Vivo Tumor Imaging

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Nanoparticles in Biomedical Imaging

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 102))

Abstract

Nanometer-sized particles, such as semiconductor quantum dots and iron oxide nanocrystals, have novel optical, electronic, magnetic, or structural properties that are not available from either individual molecules or bulk solids. When linked with tumor-targeting ligands, such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target tumor antigens (biomarkers) as well as tumor vasculatures with high affinity and specificity. In the “mesoscopic” size range of 5–100 nm diameter, quantum dots and related nanoparticles also have more surface areas and functional groups that can be linked to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Previous research has led to the development of bioaffinity nanoparticle probes for advanced molecular and cellular imaging. In this chapter, we discuss recent advances in the development and applications of bioconjugated quantum dots and multifunctional nanoparticles for in vivo tumor imaging and targeting.

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References

  • Akerman, M.E., Chan, W.C.W., Laakkonen, P., Bhatia, S.N., Ruoslahti, E., 2002. Nanocrystal targeting in vivo. Proc Natl Acad Sci USA 99, 12617–12621.

    Article  PubMed  CAS  Google Scholar 

  • Alivisatos, A.P., 1996. Semiconductor clusters, nanocrystals, and quantum dots. Science 271, 933–937.

    Article  CAS  Google Scholar 

  • Alivisatos, A.P., Gu, W.W., Larabell, C., 2005. Quantum dots as cellular probes. Annu Rev Biomed Eng 7, 55–76.

    Article  PubMed  CAS  Google Scholar 

  • Ballou, B., Lagerholm, B.C., Ernst, L.A., Bruchez, M.P., Waggoner, A.S., 2004. Noninvasive imaging of quantum dots in mice. Bioconjug Chem 15, 79–86.

    Article  PubMed  CAS  Google Scholar 

  • Bander, N.H., Trabulsi, E.J., Kostakoglu, L., Yao, D., Vallabhajosula, S., Smith-Jones, P., Joyce, M.A., Milowsky, M., Nanus, D.M., Goldsmith, S.J., 2003. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J Urol 170, 1717–1721.

    Article  PubMed  CAS  Google Scholar 

  • Bruchez, M., Moronne, M., Gin, P., Weiss, S., Alivisatos, A.P., 1998. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013–2016.

    Article  PubMed  CAS  Google Scholar 

  • Buck, S.M., Koo, Y.E.L., Park, E., Xu, H., Philbert, M.A., Brasuel, M.A., Kopelman, R., 2004. Optochemical nanosensor PEBBLEs: photonic explorers for bioanalysis with biologically localized embedding. Curr Opin Chem Biol 8, 540–546.

    Article  PubMed  CAS  Google Scholar 

  • Bulte, J.W.M., Douglas, T., Witwer, B., Zhang, S.C., Strable, E., Lewis, B.K., Zywicke, H., Miller, B., van Gelderen, P., Moskowitz, B.M., Duncan, I.D., Frank, J.A., 2001. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19, 1141–1147.

    Article  PubMed  CAS  Google Scholar 

  • Chan, W.C.W., Maxwell, D.J., Gao, X.H., Bailey, R.E., Han, M.Y., Nie, S.M., 2002. Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotechnol 13, 40–46.

    Article  PubMed  CAS  Google Scholar 

  • Chan, W.C.W., Nie, S.M., 1998. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018.

    Article  PubMed  CAS  Google Scholar 

  • Chang, S.S., Reuter, V.E., Heston, W.D.W., Gaudin, P.B., 2001. Comparison of antiprostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma. Urology 57, 1179–1183.

    Article  PubMed  CAS  Google Scholar 

  • Curtis, A., Wilkinson, C., 2001. Nantotechniques and approaches in biotechnology. Trends Biotechnol 19, 97–101.

    Article  PubMed  CAS  Google Scholar 

  • Dahan, M., Levi, S., Luccardini, C., Rostaing, P., Riveau, B., Triller, A., 2003. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302, 442–445.

    Article  PubMed  CAS  Google Scholar 

  • Derfus, A.M., Chan, W.C.W., Bhatia, S.N., 2004. Probing the cytotoxicity of semiconductor quantum dots. Nano Letters 4, 11–18.

    Article  CAS  Google Scholar 

  • Dubertret, B., Skourides, P., Norris, D.J., Noireaux, V., Brivanlou, A.H., Libchaber, A., 2002. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759–1762.

    Article  PubMed  CAS  Google Scholar 

  • Duncan, R., Discovery, N.R.D., 2003. The dawning era of polymer therapeutics. Nat Rev Drug Discov 2, 347–360.

    Article  PubMed  CAS  Google Scholar 

  • Gao, X.H., Chan, W.C.W., Nie, S.M., 2002. Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding. J Biomed Opt 7, 532–537.

    Article  PubMed  CAS  Google Scholar 

  • Gao, X.H., Cui, Y.Y., Levenson, R.M., Chung, L.W.K., Nie, S.M., 2004. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22, 969–976.

    Article  PubMed  CAS  Google Scholar 

  • Gao, X.H., Nie, S.M., 2003a. Doping mesoporous materials with multicolor quantum dots. J Phys Chem B 107, 11575–11578.

    Article  CAS  Google Scholar 

  • Gao, X.H., Nie, S.M., 2003b. Molecular profiling of single cells and tissue specimens with quantum dots. Trends Biotechnol 21, 371–373.

    Article  CAS  Google Scholar 

  • Gao, X.H., Yang, L.L., Petros, J.A., Marshal, F.F., Simons, J.W., Nie, S.M., 2005. In vivo molecular and cellular imaging with quantum dots. Curr Opin Biotechnol 16, 63–72.

    Article  PubMed  CAS  Google Scholar 

  • Gaponik, N., Radtchenko, I.L., Sukhorukov, G.B., Weller, H., Rogach, A.L., 2002. Toward encoding combinatorial libraries: Charge-driven microencapsulation of semiconductor nanocrystals luminescing in the visible and near IR. Adv Mater 14, 879–882.

    Article  CAS  Google Scholar 

  • Gref, R., Minamitake, Y., Peracchia, M.T., Trubetskoy, V., Torchilin, V., Langer, R., 1994. Biodegradable long-circulating polymeric nanospheres. Science (Washington, D. C., 1883-) 263, 1600–1603.

    Article  CAS  Google Scholar 

  • Gu, H.W., Zheng, R.K., Zhang, X.X., Xu, B., 2004. Facile one-pot synthesis of bifunctional heterodimers of nanoparticles: a conjugate of quantum dot and magnetic nanoparticles. J Am Chem Soc 126, 5664–5665.

    Article  PubMed  CAS  Google Scholar 

  • Han, M.Y., Gao, X.H., Su, J.Z., Nie, S., 2001. Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol 19, 631–635.

    Article  PubMed  CAS  Google Scholar 

  • Ishii, D., Kinbara, K., Ishida, Y., Ishii, N., Okochi, M., Yohda, M., Aida, T., 2003. Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles. Nature 423, 628–632.

    Article  PubMed  CAS  Google Scholar 

  • Jain, R.K., 1999. Understanding barriers to drug delivery: high resolution in vivo imaging is key. Clin Cancer Res 5, 1605–1606.

    PubMed  CAS  Google Scholar 

  • Jain, R.K., 2001. Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J Control Release 74, 7–25.

    Article  PubMed  CAS  Google Scholar 

  • Jaiswal, J.K., Mattoussi, H., Mauro, J.M., Simon, S.M., 2003. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol 21, 47–51.

    Article  PubMed  CAS  Google Scholar 

  • Josephson, L., Tung, C.H., Moore, A., Weissleder, R., 1999. High-efficiency intracellular magnetic labeling with novel superparamagnetic-tat peptide conjugates. Bioconjug Chem 10, 186–191.

    Article  PubMed  CAS  Google Scholar 

  • Kim, S., Lim, Y.T., Soltesz, E.G., De Grand, A.M., Lee, J., Nakayama, A., Parker, J.A., Mihaljevic, T., Laurence, R.G., Dor, D.M., Cohn, L.H., Bawendi, M.G., Frangioni, J.V., 2004. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22, 93–97.

    Article  PubMed  CAS  Google Scholar 

  • Kircher, M.F., Weissleder, R., Josephson, L., 2004. A dual fluorochrome probe for imaging proteases. Bioconjug Chem 15, 242–248.

    Article  PubMed  CAS  Google Scholar 

  • Kirchner, C., Liedl, T., Kudera, S., Pellegrino, T., Javier, A.M., Gaub, H.E., Stolzle, S., Fertig, N., Parak, W.J., 2005. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Letters 5, 331–338.

    Article  PubMed  CAS  Google Scholar 

  • Larson, D.R., Zipfel, W.R., Williams, R.M., Clark, S.W., Bruchez, M.P., Wise, F.W., Webb, W.W., 2003. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300, 1434–1436.

    Article  PubMed  CAS  Google Scholar 

  • Leatherdale, C.A., Woo, W.K., Mikulec, F.V., Bawendi, M.G., 2002. On the absorption cross section of CdSe nanocrystal quantum dots. J Phys Chem B 106, 7619–7622.

    Article  CAS  Google Scholar 

  • Lidke, D.S., Nagy, P., Heintzmann, R., Arndt-Jovin, D.J., Post, J.N., Grecco, H.E., Jares-Erijman, E.A., Jovin, T.M., 2004. Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat Biotechnol22, 198–203.

    Article  PubMed  CAS  Google Scholar 

  • Mattoussi, H., Mauro, J.M., Goldman, E.R., Anderson, G.P., Sundar, V.C., Mikulec, F.V., Bawendi, M.G., 2000. Self-assembly of CdSe-ZnS quantum dot bioconjugates using an engineered recombinant protein. J Am Chem Soc 122, 12142–12150.

    Article  CAS  Google Scholar 

  • Medintz, I.L., Clapp, A.R., Mattoussi, H., Goldman, E.R., Fisher, B., Mauro, J.M., 2003. Self-assembled nanoscale biosensors based on quantum dot FRET donors. Nat Mater 2, 630–638.

    Article  PubMed  CAS  Google Scholar 

  • Michalet, X., Pinaud, F.F., Bentolila, L.A., Tsay, J.M., Doose, S., Li, J.J., Sundaresan, G., Wu, A.M., Gambhir, S.S., Weiss, S., 2005. Quantum dots for live cells, in vivo imaging, and diagnostics. Science (Washington, D. C., 1883-) 307, 538–544.

    Article  CAS  Google Scholar 

  • Mulder, W.J.M.K., Brandwijk, R. J. Storm, G. Chin, P. T. K. Strijkers, G. J. de Mello Donega, C. Nicolay, K. Griffioen, A. W., 2006. Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Letters 6, 1–6.

    Article  PubMed  CAS  Google Scholar 

  • Ntziachristos, V., Bremer, C., Weissleder, R., 2003. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 13, 195–208.

    PubMed  Google Scholar 

  • Ntziachristos, V., Schellenberger, E.A., Ripoll, J., Yessayan, D., Graves, E., Bogdanov, A., Josephson, L., Weissleder, R., 2004. Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate. Proc Natl Acad SciUSA 101, 12294–12299.

    Article  CAS  Google Scholar 

  • Patri, A.K., Myc, A., Beals, J., Thomas, T.P., Bander, N.H., Baker, J.R., 2004. Synthesis and in vitro testing of J591 antibody-dendrimer conjugates for targeted prostate cancer therapy. Bioconjug Chem 15, 1174–1181.

    Article  PubMed  CAS  Google Scholar 

  • Pinaud, F., et al., 2006. Advances in fluorescence imaging with quantum dot bio-probes. Biomaterials 27, 1679–1687.

    Article  PubMed  CAS  Google Scholar 

  • Quintana, A., Raczka, E., Piehler, L., Lee, I., Myc, A., Majoros, I., Patri, A.K., Thomas, T., Mule, J., Baker, J.R., 2002. Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm Res 19, 1310–1316.

    Article  PubMed  CAS  Google Scholar 

  • Schellenberger, E.A., Sosnovik, D., Weissleder, R., Josephson, L., 2004. Magneto/optical annexin V, a multimodal protein. Bioconjug Chem 15, 1062–1067.

    Article  PubMed  CAS  Google Scholar 

  • Smith, A., Ruan, G., Rhyner,M.N., Nie, S.M., 2006. Engineering luminescent quantum dots for in vivo molecular and cellular imaging. Ann Biomed Eng 34, 1–12.

    Article  Google Scholar 

  • Smith, A.M., Gao, X.H., Nie, S.M., 2004. Quantum dot nanocrystals for in vivo molecular and cellular imaging. Photochem Photobiol 80, 377–385.

    PubMed  CAS  Google Scholar 

  • Stroh, M., Zimmer, J.P., Duda, D.G., Levchenko, T.S., Cohen, K.S., Brown, E.B., Scadden, D.T., Torchilin, V.P., Bawendi, M.G., Fukumura, D., Jain, R.K., 2005. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 11, 678–682.

    Article  PubMed  CAS  Google Scholar 

  • Torchilin, V., Babich, J., Weissig, V., 2000. Liposomes and micelles to target the blood pool for imaging purposes. J Liposome Res 10, 483–499.

    Article  CAS  Google Scholar 

  • Torchilin, V.P., Trubetskoy, V.S., Milshteyn, A.M., Canillo, J., Wolf, G.L., Papisov, M.I., Bogdanov, A.A., Narula, J., Khaw, B.A., Omelyanenko, V.G., 1994. Targeted delivery of diagnostic agents by surface-modified liposomes. J Control Release 28, 45–58.

    Article  CAS  Google Scholar 

  • Wang, D.S., He, J.B., Rosenzweig, N., Rosenzweig, Z., 2004. Superparamagnetic Fe2O3 Beads-CdSe/ZnS quantum dots core-shell nanocomposite particles for cell separation. Nano Letters 4, 409–413.

    Article  CAS  Google Scholar 

  • Wu, X.Y., Liu, H.J., Liu, J.Q., Haley, K.N., Treadway, J.A., Larson, J.P., Ge, N.F., Peale, F., Bruchez, M.P., 2003. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol 21, 41–46.

    Article  PubMed  CAS  Google Scholar 

  • Xu HX, S.M., Wong, E.Y., et al., 2003. Multiplexed SNP genotyping using the Qbead (TM) system: a quantum dot-encoded microsphere-based assay. Nucleic Acids Res 31, e43.

    Article  PubMed  Google Scholar 

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Rhyner, M.N., Smith, A.M., Gao, X., Mao, H., Yang, L., Nie, S. (2008). Quantum Dots and Targeted Nanoparticle Probes for In Vivo Tumor Imaging. In: Bulte, J.W., Modo, M.M. (eds) Nanoparticles in Biomedical Imaging. Fundamental Biomedical Technologies, vol 102. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72027-2_19

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