Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo

Larson, Daniel R.; Zipfel, Warren R.; Williams, Rebecca M.; Clark, Stephen W.; Bruchez, Marcel P.; Wise, Frank W.; Webb, Watt W.

doi:10.1126/science.1083780

Cited by 2,158 publications

(1,404 citation statements)

References 20 publications

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“…Fluorescence imaging as a safe, cost‐effective modality with high temporal and spatial resolution appears to be one of the indispensable platforms 3, 4. In particularly, fluorescent nanoparticles (NPs) covalently linked with biorecognition ligands have shown great merits in cancer diagnosis and therapy 5, 6, 7, 8.…”

Section: Introductionmentioning

confidence: 99%

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Feng

Liu

et al. 2017

Advanced Science

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Fluorescent and biocompatible organic nanoparticles have attracted great interest in cancer detection and imaging, but the nonspecific cellular uptake has limited the detection specificity and sensitivity. Herein, the authors report the ultrasmall conjugated polymer nanoparticles (CPNs) with bright far‐red/near‐infrared emission for targeted cancer imaging with high specificity. The sizes of the ultrasmall CPNs are around 6 nm (CPN6), while large CPNs show sizes around 30 nm (CPN30). Moreover, CPN6 exhibits largely improved fluorescence quantum yield (η) of 41% than CPN30 (25%). Benefiting from the ultrasmall size, bare CPN6 shows largely suppressed nonspecific cellular uptake as compared to CPN30, while cyclic arginine‐glycine‐aspartic acid (cRGD) functionalized CPN6 (cRGD‐CPN6) possesses excellent selectivity toward αvβ 3 integrin overexpressed MDA‐MB‐231 cells over other cells in cell mixtures. The faster body clearance of CPN6 over CPN30 indicates its greater potentials as a noninvasive nanoprobe for in vivo and practical applications.

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Section: Introductionmentioning

confidence: 99%

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Feng

Liu

et al. 2017

Advanced Science

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“…Depending on the nature of this coupling, the ground state or the excited state may be either localized or delocalized, and specific optical properties may be either enhanced or suppressed. 44 Among the many NLO effects, two-photon absorption (TPA) has become very popular during the past decade owing to its wide-ranging applications such as two-photon laser scanning microscopy, [45][46][47] photodynamic therapy, 48 optical power limitation, 4,5 microfabrication, [49][50][51][52] or 3D optical data storage. [53][54][55][56] Depending on the applications, two-photon chromophores have to satisfy different kinds of requirements.…”

Section: Introductionmentioning

confidence: 99%

Effects of (Multi)branching of Dipolar Chromophores on Photophysical Properties and Two-Photon Absorption

et al. 2005

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To investigate the effect of branching on linear and nonlinear optical properties, a specific series of chromophores, epitome of (multi)branched dipoles, has been thoroughly explored by a combined theoretical and experimental approach. Excited-state structure calculations based on quantum-chemical techniques (timedependent density functional theory) as well as a Frenkel exciton model nicely complement experimental photoluminescence and one-and two-photon absorption findings and contribute to their interpretation. This allowed us to get a deep insight into the nature of fundamental excited-state dynamics and the nonlinear optical (NLO) response involved. Both experiment and theory reveal that a multidimensional intramolecular charge transfer takes place from the donating moiety to the periphery of the branched molecules upon excitation, while fluorescence stems from an excited state localized on one of the dipolar branches. Branching is also observed to lead to cooperative enhancement of two-photon absorption (TPA) while maintaining high fluorescence quantum yield, thanks to localization of the emitting state. The comparison between results obtained in the Frenkel exciton scheme and ab initio results suggests the coherent coupling between branches as one of the possible mechanisms for the observed enhancement. New strategies for the rational design of NLO molecular assemblies are thus inferred on the basis of the acquired insights.

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“…Despite tremendous developments in the field of fluorescent dyes, certain disadvantages such as photobleaching have yet not been overcome. In the last decade, a new generation of biomarkers has emerged in the form of quantum dots (1,2) and metal, especially gold nanoparticles (GNPs) (3,4). Neither is limited by photobleaching anymore.…”

Section: Introductionmentioning

confidence: 99%

Nonendosomal cellular uptake of ligand‐free, positively charged gold nanoparticles

et al. 2010

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Gold nanoparticles (GNPs) have interesting optical properties, such as exceptionally high quantum yields and virtually limitless photostability. Therefore, they show the potential for applications as biomarkers especially suitable for in vivo and long-term studies. The generation of GNPs using pulsed laser light rather than chemical means provides nanoparticles, which are remarkably stable in a variety of media without the need of stabilizing agents or ligands. This stabilization is achieved by partial oxidation of the gold surface resulting in positively charged GNPs. However, little is known about cellular uptake of such ligand-free nanoparticles, their intracellular fate, or cell viability after nanoparticle contact. The current work is aimed to explore the response of a bovine cell line to GNP exposure mainly using laser scanning confocal microscopy (LSCM) supported by other techniques. Cultured bovine immortalized cells (GM7373) were coincubated with GNP (average diameter 15 nm, 50 lM Au) for 2, 24, and 48 h. The detection of GNP-associated light scattering by the LSCM facilitated a clear distinction between GNP-containing cells and the negative controls. After 48 h, 75% of cells had visibly incorporated nanoparticles. No colocalization was detected with either Rab5a or Lamp1-positive structures, i.e., endosomes or lysosomes, respectivley. However, transmission electron microscope analysis of GNP-coincubated cells indicated the nanoparticles to be positioned within electron-dense structures. Coincubation at 48C did not inhibit nanoparticle uptake, suggesting diffusion as possible entrance mechanism. Although the assessment of cell morphology, membrane integrity, and apoptosis revealed no GNP-related loss of cell viability at a gold concentration of 25 lM or below, a cytotoxic effect was observed in a proliferation assay after exposing low cell numbers to 50 lM Au and above. In conclusion, this study confirmed the cellular uptake of ligand-free gold nanoparticles during coincubation apparently without using endocytic pathways. '

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Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo

Cited by 2,158 publications

References 20 publications

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Effects of (Multi)branching of Dipolar Chromophores on Photophysical Properties and Two-Photon Absorption

Nonendosomal cellular uptake of ligand‐free, positively charged gold nanoparticles

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