ZrO(HPO4)1−x(FMN)x: Quick and Easy Synthesis of a Nanoscale Luminescent Biomarker

Roming, Marcus; Lünsdorf, Heinrich; Dittmar, Kurt E.J.; Feldmann, Claus

doi:10.1002/anie.200902893

Cited by 33 publications

(13 citation statements)

References 37 publications

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“…For this purpose, NPs can be loaded with multiple fluorescent dyes or used as MRI or CT contrast agents 14,20-22. Recently, we have introduced inorganic-organic hybrid NPs (IOH-NPs) as a novel group of multifunctional NPs, which can easily incorporate versatile functions such as drug transport and delivery together with NP tracking using fluorescence imaging, MRI or photoacoustic imaging (PAI) 22-24. Our previous in vitro findings that fluorescent IOH-NPs containing the GC betamethasone phosphate (BMP) are taken up by macrophages and efficiently reduce pro-inflammatory cytokine TNFα production in stimulated mouse macrophages made them attractive for in vivo applications 23.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites

et al. 2018

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Treatment of inflammatory disorders with glucocorticoids (GCs) is often accompanied by severe adverse effects. Application of GCs via nanoparticles (NPs), especially those using simple formulations, could possibly improve their delivery to sites of inflammation and therefore their efficacy, minimising the required dose and thus reducing side effects. Here, we present the evaluation of NPs composed of GC betamethasone phosphate (BMP) and the fluorescent dye DY-647 (BMP-IOH-NPs) for improved treatment of inflammation with simultaneous in vivo monitoring of NP delivery.Methods: BMP-IOH-NP uptake by MH-S macrophages was analysed by fluorescence and electron microscopy. Lipopolysaccharide (LPS)-stimulated cells were treated for 48 h with BMP-IOH-NPs (1×10-5-1×10-9 M), BMP or dexamethasone (Dexa). Drug efficacy was assessed by measurement of interleukin 6. Mice with Zymosan-A-induced paw inflammation were intraperitoneally treated with BMP-IOH-NPs (10 mg/kg) and mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI) were treated intranasally with BMP-IOH-NPs, BMP or Dexa (each 2.5 mg/kg). Efficacy was assessed in vivo by paw volume measurements with µCT and ex vivo by measurement of paw weight for Zymosan-A-treated mice, or in the AAI model by in vivo x-ray-based lung function assessment and by cell counts in the bronchoalveolar lavage (BAL) fluid and histology. Delivery of BMP-IOH-NPs to the lungs of AAI mice was monitored by in vivo optical imaging and by fluorescence microscopy.Results: Uptake of BMP-IOH-NPs by MH-S cells was observed during the first 10 min of incubation, with the NP load increasing over time. The anti-inflammatory effect of BMP-IOH-NPs in vitro was dose dependent and higher than that of Dexa or free BMP, confirming efficient release of the drug. In vivo, Zymosan-A-induced paw inflammation was significantly reduced in mice treated with BMP-IOH-NPs. AAI mice that received BMP-IOH-NPs or Dexa but not BMP revealed significantly decreased eosinophil numbers in BALs and reduced immune cell infiltration in lungs. Correspondingly, lung function parameters, which were strongly affected in non-treated AAI mice, were unaffected in AAI mice treated with BMP-IOH-NPs and resembled those of healthy animals. Accumulation of BMP-IOH-NPs within the lungs of AAI mice was detectable by optical imaging for at least 4 h in vivo, where they were preferentially taken up by peribronchial and alveolar M2 macrophages.Conclusion: Our results show that BMP-IOH-NPs can effectively be applied in therapy of inflammatory diseases with at least equal efficacy as the gold standard Dexa, while their delivery can be simultaneously tracked in vivo by fluorescence imaging. BMP-IOH-NPs thus have the potential to reach clinical applications.

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Section: Introductionmentioning

confidence: 99%

Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites

et al. 2018

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“…However, the PL is conned to low UV excitation wavelengths and thus any application using common uorescence microscopes is seriously compromised. [27][28][29][30] Here we show that a wet-chemical surface functionalization step of monodisperse $5 nm zirconia nanoparticles (ZrO 2 NPs) leads to a signicant shi of the emission in a spectral range that is particularly useful for bioimaging (e.g. probing events at a cellular level) in the visible range.…”

Section: Introductionmentioning

confidence: 99%

Amine functionalized ZrO₂nanoparticles as biocompatible and luminescent probes for ligand specific cellular imaging

et al. 2015

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“…[17][18][19][20][21][22] When these materials are scaled down to the nano-regime to afford nanoscale coordination polymers (NCPs), they can be exploited for a number of biomedical applications. [23][24][25][26] For example, we and others have demonstrated the potential utility of NCPs in magnetic resonance imaging, [27][28][29][30][31][32] computed tomography, 33 optical imaging, 34,35 and biosensing. 36 Whereas Horcajada and coworkers demonstrated the delivery of chemotherapeutics in the pores of the MIL family of NCPs, 37,38 our group successfully delivered cisplatin prodrugs by either direct incorporation of the prodrug into an NCP or postsynthetic covalent attachment of a prodrug to a pre-synthesized NCP.…”

Section: Introductionmentioning

confidence: 99%

Lipid-coated nanoscale coordination polymers for targeted delivery of antifolates to cancer cells

et al. 2012

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Nanoscale coordination polymers (NCPs) have been demonstrated as an interesting platform for drug delivery, as they possess many advantages over small-molecule chemotherapeutics, such as high payloads, lower systemic toxicity, tunability, and enhanced tumor uptake. Existing formulations for the delivery of methotrexate (MTX), an antifolate cancer drug, have very low drug loadings. Herein, we report the incorporation of MTX as a building block in an NCP formulation with exceptionally high drug loadings (up to 79.1 wt%) and the selective delivery of the NCP to cancer cells. Encapsulation of the NCP in a functionalized lipid bilayer allows for targeted delivery and controlled release to cancer cells. A phosphor can be doped into the NCPs for monitoring particle uptake by optical imaging. The lipid-coated and anisamide-targeted NCPs have superior in vitro efficacy against acute lymphoblastic leukemia cells when compared to free drug.

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ZrO(HPO₄)_1−x(FMN)_x: Quick and Easy Synthesis of a Nanoscale Luminescent Biomarker

Cited by 33 publications

References 37 publications

Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites

Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites

Amine functionalized ZrO₂nanoparticles as biocompatible and luminescent probes for ligand specific cellular imaging

Lipid-coated nanoscale coordination polymers for targeted delivery of antifolates to cancer cells

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ZrO(HPO4)1−x(FMN)x: Quick and Easy Synthesis of a Nanoscale Luminescent Biomarker

Cited by 33 publications

References 37 publications

Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites

Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites

Amine functionalized ZrO2nanoparticles as biocompatible and luminescent probes for ligand specific cellular imaging

Lipid-coated nanoscale coordination polymers for targeted delivery of antifolates to cancer cells

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Product

Resources

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ZrO(HPO₄)_1−x(FMN)_x: Quick and Easy Synthesis of a Nanoscale Luminescent Biomarker

Amine functionalized ZrO₂nanoparticles as biocompatible and luminescent probes for ligand specific cellular imaging