FMN-coated fluorescent iron oxide nanoparticles for RCP-mediated targeting and labeling of metabolically active cancer and endothelial cells

Jayapaul, Jabadurai; Hodenius, Michael; Arns, Susanne; Lederle, Wiltrud; Lammers, Twan; Comba, Peter; Gaetjens, Jessica

doi:10.1016/j.biomaterials.2011.04.056

Cited by 62 publications

(68 citation statements)

References 35 publications

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“…USPIO nanoparticles were synthesized by coprecipitation of ferrous (Fe 2+ ) and ferric (Fe 3+ ) salts under aqueous alkaline conditions as previously described [17,18]. Briefly, in a stoichiometric ratio of 2Fe 3+ :Fe 2+ , 16 mmol (2.66 g) FeCl 3 and 8 mmol (1.63 g) FeCl 2 ·4H 2 O dissolved in 190 mL de-ionized water were co-precipitated using 10 mL 25% NH 3 .…”

Section: Synthesis Of Iron Oxide Nanoparticles (Fe 3 O 4 )mentioning

confidence: 99%

“…FLUSPIO nanoparticles were prepared as previously described [17]. Briefly, 143 mM USPIO (pH 4) was sonicated with 35 mM FMN for 1 h at ambient temperature.…”

Section: Synthesis Of Fluspio Nanoparticlesmentioning

confidence: 99%

“…In the competitive-binding group (n = 5), mice were injected with 10-fold excess FMN at 10 min before FLUSPIO (900 μmol Fe/kg) administration. MR imaging of LnCap tumor xenografts pre-and post-particle injection (1 and 3 h) was performed under isoflurane anesthesia (2%) using a clinical 3T MRI system (Philips Achieva 3.0 T), in combination with a custom-built small animal solenoid sense-receive mouse coil [17].…”

Section: Mr Imaging Of Fluspio Accumulation In Lncap Xenografts In Micementioning

confidence: 99%

“…Therefore, to achieve colloidal stability and sustain FMN fluorescence without quenching under aqueous conditions, the surface of USPIO nanoparticles was additionally covered with non-toxic and biocompatible GMP. We previously demonstrated that a ratio of 0.7:0.3 between GMP and FMN molecules is needed to expedite complete coverage of USPIO nanoparticle surface [17]. Figures S1(a) and S1(b) in the Electronic Supplementary Material (ESM) show a schematic sketch of the adsorptive coating of USPIO using FMN and GMP.…”

Section: Fluspio Synthesismentioning

confidence: 99%

“…Therefore, we designed RCP-targeted, fluorescent USPIO (FLUSPIO) as a contrast agent for magnetic resonance imaging (MRI) and demonstrated its ability to label metabolically active cancer cells as well as activated endothelial cells [17]. In another previous study, we developed a second MRI probe, FAD-USPIO, to assess vascular metabolism in prostate tumors [18].…”

Section: Introductionmentioning

confidence: 99%

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In vivo evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

et al. 2016

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Riboflavin (Rf) receptors bind and translocate Rf and its phosphorylated forms (e.g. flavin mononucleotide, FMN) into cells where they mediate various cellular metabolic pathways. Previously, we showed that FMN-coated ultrasmall superparamagnetic iron oxide (FLUSPIO) nanoparticles are suitable for labeling metabolically active cancer and endothelial cells in vitro. In this study, we focused on the in vivo application of FLUSPIO using prostate cancer xenografts. Size, charge, and chemical composition of FLUSPIO were evaluated. We explored the in vitro specificity of FLUSPIO for its cellular receptors using magnetic resonance imaging (MRI) and Prussian blue staining. Competitive binding experiments were performed in vivo by injecting free FMN in excess. Bio-distribution of FLUSPIO was determined by estimating iron content in organs and tumors using a colorimetric assay. AFM analysis and zeta potential measurements revealed a particulate morphology approximately 20-40 nm in size and a negative zeta potential (-24.23 ± 0.15 mV) in water. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry data confirmed FMN present on the USPIO nanoparticle surface. FLUSPIO uptake in prostate cancer cells and human umbilical vein endothelial cells was significantly higher than that of control USPIO, while addition of excess of free FMN reduced accumulation. Similarly, in vivo MRI and histology showed specific FLUSPIO uptake by prostate cancer cells, tumor endothelial cells, and tumor-associated macrophages. Besides prominent tumor accumulation, FLUSPIO accumulated in the liver, spleen, lung, and skin. Hence, our data strengthen our hypothesis that targeting riboflavin receptors is an efficient approach to accumulate nanomedicines in tumors opening perspectives for the development of diagnostic and therapeutic systems.

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Section: Synthesis Of Iron Oxide Nanoparticles (Fe 3 O 4 )mentioning

confidence: 99%

“…FLUSPIO nanoparticles were prepared as previously described [17]. Briefly, 143 mM USPIO (pH 4) was sonicated with 35 mM FMN for 1 h at ambient temperature.…”

Section: Synthesis Of Fluspio Nanoparticlesmentioning

confidence: 99%

Section: Mr Imaging Of Fluspio Accumulation In Lncap Xenografts In Micementioning

confidence: 99%

Section: Fluspio Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

et al. 2016

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Theranostic USPIO‐Loaded Microbubbles for Mediating and Monitoring Blood‐Brain Barrier Permeation

Lammers

Koczera

Fokong

et al. 2014

Adv Funct Materials

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131

109

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Efficient and safe drug delivery across the blood-brain barrier (BBB) remains to be one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, we show that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO-MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non-invasive R*-based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R* relaxometry were in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug FITC-dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB, and for enabling safe and efficient treatment of CNS disorders.

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Novel Biological Functions of ZIF‐NP as a Delivery Vehicle: High Pulmonary Accumulation, Favorable Biocompatibility, and Improved Therapeutic Outcome

Wang

Shi

et al. 2016

Adv Funct Materials

136

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Though zeolitic imidazole framework (ZIF) emerges as an advanced functional material for small-molecule delivery due to its unique features such as high loading and pH-sensitive degradation, there are extreme short of knowledge regarding its biological functions. To qualify this category of delivery vehicle, ZIF-8 nanoparticles (ZIF-NPs) with or without cargo are engineered and comprehensively investigated in vitro and in vivo. Interestingly, ZIF-NPs demonstrate strong bioadhesion but with limited internalization themselves, which enhance the membrane-mediated ROS and are different from that of inorganic ZnO inducing mitochondria-mediated reactive oxygen species (ROS) without biomembrane damage. Unexpected high concentration is found in lung, probably due to the particle size and distribution of the nanocarriers; however, the drug levels drop dramatically with time, revealing the fast degradation and elimination. At the given doses, ZIF-NPs exhibit reasonably biosafety in animal tests as evidenced by their acceptable system and blood biocompatibilities, and minimal impacts on the liver and renal functions, immune cells, infl ammatory factors, etc. ZIF-NPs with fl uorouracil loading (5F@ZIF-NPs) signifi cantly improve the therapeutic outcome of lung metastasis tumor in a nude mice model. Generally, ZIF-NPs demonstrate unique biological functions in terms of bio-nano interaction, pulmonary accumulation, biocompatibility, and antitumor therapy, which endow them potential as the delivery vehicles.

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FMN-coated fluorescent iron oxide nanoparticles for RCP-mediated targeting and labeling of metabolically active cancer and endothelial cells

Cited by 62 publications

References 35 publications

In vivo evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

In vivo evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

Theranostic USPIO‐Loaded Microbubbles for Mediating and Monitoring Blood‐Brain Barrier Permeation

Novel Biological Functions of ZIF‐NP as a Delivery Vehicle: High Pulmonary Accumulation, Favorable Biocompatibility, and Improved Therapeutic Outcome

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