In vivo cancer targeting and imaging with semiconductor quantum dots

Gao, Xiaohu; Cui, Yuanyuan; Levenson, Richard M.; Chung, Leland W.K.; Nie, Shuming

doi:10.1038/nbt994

Cited by 4,499 publications

(3,331 citation statements)

References 55 publications

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“…reported (20) to be 20-50 ns and that of the EuMac in the dry state is~2 ms; thus, the half-life of the EuMac is 40,000-100,000 times longer than that of a quantum dot. Accordingly, for each time-gated image, the exposure time used for the EuMac or any other long-lived lanthanide ion complex can be 40,000-100,000 times longer than that for a quantum dot.…”

Section: Discussionmentioning

confidence: 96%

Increasing lanthanide luminescence by use of the RETEL effect

et al. 2006

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Background: Luminescent lanthanide complexes produce emissions with the narrowest-known width at half maximum; however, their significant use in cytometry required an increase in luminescence intensity. The companion review, Leif et al., Cytometry 2006;69A:767-778, described a new technique for the enhancement of lanthanide luminescence, the Resonance Energy Transfer Enhanced Luminescence (RETEL) effect, which increases luminescence and is compatible with standard slide microscopy. Methods: The luminescence of the europium ion macrocyclic complex, EuMac, was increased by employing the RETEL effect. After adding the nonluminescent gadolinium ion complex of the thenoyltrifluoroacetonate (TTFA) ligand or the sodium salt of TTFA in ethanol solution, the EuMac-labeled sample was allowed to dry. Both a conventional arc lamp and a time-gated UV LED served as light sources for microscopic imaging. The emission intensity was measured with a CCD camera. Multiple time-gated images were summed with special software to permit analysis and effective presentation of the final image.Results: With the RETEL effect, the luminescence of the EuMac-streptavidin conjugate increased at least six-fold upon drying. Nuclei of apoptotic cells were stained with DAPI and tailed with 5BrdUrd to which a EuMac-anti5BrdU conjugate was subsequently attached. Time-gated images showed the long-lived EuMac luminescence but did not show the short-lived DAPI fluorescence. Imaging of DNA-synthesizing cells with an arc lamp showed that both S phase and apoptotic cells were labeled, and that their labeling patterns were different. The images of the luminescent EuMac and fluorescent DAPI were combined to produce a color image on a white background. This combination of simple chemistry, instrumentation, and presentation should make possible the inexpensive use of the lanthanide macrocycles, Quantum Dyes Ò , as molecular diagnostics for cytological and histopathological microscopic imaging. q 2006 International Society for Analytical Cytology Key terms: quantum dye; columinescence; RETEL; lanthanide; macrocycle; luminescence; time-delayed; europium; terbium Lanthanide ion complexes have found a variety of significant applications in laboratory diagnostics (1-3); however, the weak luminescence of these complexes, which is due to their comparatively low molar extinction coefficients (molar absorptivities), was a major impediment to their use in cytometry (4). The problem of increasing the emission intensity of lanthanide ion complexes has been solved by the use of the resonance energy transfer enhanced luminescence (RETEL) effect, formerly called FRE-TEL (5), combined with measurement in the dry state. In the RETEL effect, as described by Leif, Vallarino, and coworkers in the companion Review article published in this issue of Cytometry (6), light energy originally absorbed by a nonluminescent photon acceptor (a complex or an unbound ligand) is transferred to the central lanthanide ion of a macrocyclic complex, Quantum Dye Ò , thus enhancing its emission int...

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Section: Discussionmentioning

confidence: 96%

Increasing lanthanide luminescence by use of the RETEL effect

et al. 2006

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“…Although integrating nano-bioimaging technology and therapeutic medical application using multifunctional nanoparticles or nanomaterials poses a significant challenge, this can provide a novel approach in biomedicine such as simultaneous delivery of imaging and therapeutic agents (Gao et al, 2004;Michalet et al, 2005).…”

Section: Nanodevices As Extracellular Matrix-mimicrymentioning

confidence: 99%

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

Kim

Ahn

Chung

et al. 2013

Molecules and Cells

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Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnologybased materials and living cells in both in vitro and in vivo settings.

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“…For optical imaging, nanoparticles can be loaded with fluorescent dyes that emit light of different wavelengths, which permits multiplexed imaging of various properties of the tumor tissue in one examination ( Figure 2B). 21 Optimization of the pharmacokinetics of nanoparticles is, however, still an issue, especially reduction of their accumulation by the reticuloendothelial system in the liver and spleen.…”

Section: Imaging Of Target Expressionmentioning

confidence: 99%

Technology Insight: novel imaging of molecular targets is an emerging area crucial to the development of targeted drugs

et al. 2008

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SUMMARYTargeted drugs hold great promise for the treatment of malignant tumors; however, there are several challenges for efficient evaluation of these drugs in preclinical and clinical studies. These challenges include identifying the 'correct', biologically active concentration and dose schedule, selecting the patients likely to benefit from treatment, monitoring inhibition of the target protein or pathway, and assessing the response of the tumor to therapy. Although anatomic imaging will remain important, molecular imaging provides several new opportunities to make the process of drug development more efficient. Various techniques for molecular imaging that enable noninvasive and quantitative imaging are now available in the preclinical and clinical settings, to aid development and evaluation of new drugs for the treatment of cancer. In this Review, we discuss the integration of molecular imaging into the process of drug development and how molecular imaging can address key questions in the preclinical and clinical evaluation of new targeted drugs. Examples include imaging of the expression and inhibition of drug targets, noninvasive tissue pharmacokinetics, and early assessment of the tumor response.

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In vivo cancer targeting and imaging with semiconductor quantum dots

Cited by 4,499 publications

References 55 publications

Increasing lanthanide luminescence by use of the RETEL effect

Increasing lanthanide luminescence by use of the RETEL effect

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

Technology Insight: novel imaging of molecular targets is an emerging area crucial to the development of targeted drugs

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