The contribution of the capillary endothelium to blood clearance and tissue deposition of anionic quantum dots in vivo

Praetner, Marc; Rehberg, Markus; Bihari, Péter; Lerchenberger, Maximilian; Uhl, Bernd; Holzer, Martin; Eichhorn, Martin; Fürst, Robert; Perisic, Tamara; Reichel, Christoph; Welsch, Ulrich; Krombach, Fritz

doi:10.1016/j.biomaterials.2010.05.051

Cited by 45 publications

(52 citation statements)

References 42 publications

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“…As could be expected on the basis of previous studies with nonmodified (32,33) as well as RGD-modified Qdots (34), the major part of the injected dose (ID) was sequestered into the liver and spleen (Table S1). Highly interesting was the particle content in the eye.…”

Section: Resultssupporting

confidence: 73%

Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application

Pollinger¹,

Hennig²,

Ohlmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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To date, diseases affecting vascular structures in the posterior eye are mostly treated by laser photocoagulation and multiple intraocular injections, procedures that destroy healthy tissue and can cause vision-threatening complications. To overcome these drawbacks, we investigate the feasibility of receptor-mediated nanoparticle targeting to capillary endothelial cells in the retina after i.v. application. Cell-binding studies using microvascular endothelial cells showed receptor-specific binding and cellular uptake of cyclo(RGDfC)-modified quantum dots via the αvβ3 integrin receptor. Conversely, Mueller cells and astrocytes, representing off-target cells located in the retina, revealed only negligible interaction with nanoparticles. In vivo experiments, using nude mice as the model organism, demonstrated a strong binding of the ligand-modified quantum dots in the choriocapillaris and intraretinal capillaries upon i.v. injection and 1-h circulation time. Nontargeted nanoparticles, in contrast, did not accumulate to a significant amount in the target tissue. The presented strategy of targeting integrin receptors in the retina could be of utmost value for future intervention in pathologies of the posterior eye, which are to date only accessible with difficulty.age-related macular degeneration | diabetic retinopathy | choroid | neovascularization | ligand receptor interaction

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Section: Resultssupporting

confidence: 73%

Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application

Pollinger¹,

Hennig²,

Ohlmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The relatively low TOPO-PMAT QD uptake observed in the present study with the A549 and SVEC cell lines was not unexpected as these cells are not necessarily known to be particle scavengers. However, Praetner and colleagues (2010) have recently shown that QD nanoparticles can be taken up in vivo by capillary endothelial cells. Because these epithelial and endothelial type cells would potentially be exposed to QDs following intravenous administration for medical purposes, examination of the potential QD mediated toxicity in an additional battery of assays was warranted.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase expression as a biomarker of exposure to amphiphilic polymer-coated CdSe/ZnS quantum dots

et al. 2012

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Because of their unique optical properties quantum dots (QDs) have become a preferred system for ultrasensitive detection and imaging. However, since QDs commonly contain Cd and other heavy metals, concerns have been raised regarding their toxicity. QDs are thus commonly synthesized with a ZnS cap structure, and/or coated with polymeric stabilizers. We recently synthesized amphiphilic polymer coated TOPO-PMAT QDs which are highly stable in aqueous environments. The effects of these QDs on viability and stress response in five cell lines of mouse and human origins are reported here. Human and mouse macrophages, and human kidney cells readily internalized these QDs, resulting in modest toxicity. TOPO-PMAT QD exposure was highly correlated with the induction of the stress response protein heme oxygenase-1 (HMOX1). Other stress biomarkers (glutamate cysteine ligase modifier subunit, NAD(P)H, necrosis) were only moderately affected. HMOX1 may thus be a useful biomarker of TOPO-QDOT QD exposure across cell types and species.

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“…Therefore, anionic QDs have a relatively low residence time in the blood stream and preferably accumulate in organs. 505 On the other hand it was also shown that high doses of QDs could cause pulmonary vascular thrombosis by triggering the coagulation cascade via contact activation. 506 Understanding the interaction of QDs with blood cells would help to improve QD design for theranostic drug delivery purposes.…”

Section: In Vivo Investigationsmentioning

confidence: 99%

Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors

2015

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Semiconductor quantum dots (QDs) have become important fluorescent probes for in vitro and in vivo bioimaging research. Their nanoparticle surfaces for versatile bioconjugation, their adaptable photophysical properties for multiplexed detection, and their superior stability for longer investigation times are the main advantages of QDs compared to other fluorescence imaging agents. Here, we review the recent literature dealing with the design and application of QD-bioconjugates for advanced in vitro and in vivo imaging. After a short summary of QD preparation and their most important properties, different QD-based imaging applications will be discussed from the technological and the biological point of view, ranging from super-resolution microscopy and single-particle tracking over in vitro cell and tissue imaging to in vivo investigations. A substantial part of the review will focus on multifunctional applications, in which the QD fluorescence is combined with drug or gene delivery towards theranostic approaches or with complementary technologies for multimodal imaging. We also briefly discuss QD toxicity issues and give a short outlook on future directions of QD-based bioimaging.

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The contribution of the capillary endothelium to blood clearance and tissue deposition of anionic quantum dots in vivo

Cited by 45 publications

References 42 publications

Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application

Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application

Heme oxygenase expression as a biomarker of exposure to amphiphilic polymer-coated CdSe/ZnS quantum dots

Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors

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