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-co...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.展开更多
In this study,the influence of a plasma electrolytic oxidation(PEO)surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the eff...In this study,the influence of a plasma electrolytic oxidation(PEO)surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion features and mechanical properties throughout the corrosion process.First,a comprehensive in-vitro immersion study was performed on WE43-based tensile specimens with and without PEO surface modification,which included fully automated spatial reconstruction of the phenomenological features of corrosion through micro-CT scanning,followed by uniaxial tensile testing.Then the experimental data of both unmodified and PEO-modified groups were used to calibrate parameters of a finite element-based surface corrosion model.In-vitro,it was found that the WE43-PEO modified group had a significantly lower corrosion rate and maintained significantly higher mechanical properties than the unmodified.While corrosion rates were~50%lower in the WE43-PEO modified specimens,the local geometric features of corroding surfaces remained similar to the unmodified WE43 group,however evolving after almost the double amount of time.We were also able to quantitatively demonstrate that the PEO surface treatment on magnesium continued to protect samples from corrosion throughout the entire period tested,and not just in the early stages of corrosion.Using the results from the testing framework,the model parameters of the surface-based corrosion model were identified for both groups.This enabled,for the first time,in-silico prediction of the physical features of corrosion and the mechanical performance of both unmodified and PEO modified magnesium specimens.This simulation framework can enable future in-silico design and optimisation of bioabsorbable magnesium devices for load-bearing medical applications.展开更多
文摘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.
基金Funding support was also provided by the Irish Research Council(IRC)Government of Ireland Postgraduate Scholarship(GOIPG/2017/2102).
文摘In this study,the influence of a plasma electrolytic oxidation(PEO)surface treatment on a medical-grade WE43-based magnesium alloy is examined through an experimental and computational framework that considers the effects of localised corrosion features and mechanical properties throughout the corrosion process.First,a comprehensive in-vitro immersion study was performed on WE43-based tensile specimens with and without PEO surface modification,which included fully automated spatial reconstruction of the phenomenological features of corrosion through micro-CT scanning,followed by uniaxial tensile testing.Then the experimental data of both unmodified and PEO-modified groups were used to calibrate parameters of a finite element-based surface corrosion model.In-vitro,it was found that the WE43-PEO modified group had a significantly lower corrosion rate and maintained significantly higher mechanical properties than the unmodified.While corrosion rates were~50%lower in the WE43-PEO modified specimens,the local geometric features of corroding surfaces remained similar to the unmodified WE43 group,however evolving after almost the double amount of time.We were also able to quantitatively demonstrate that the PEO surface treatment on magnesium continued to protect samples from corrosion throughout the entire period tested,and not just in the early stages of corrosion.Using the results from the testing framework,the model parameters of the surface-based corrosion model were identified for both groups.This enabled,for the first time,in-silico prediction of the physical features of corrosion and the mechanical performance of both unmodified and PEO modified magnesium specimens.This simulation framework can enable future in-silico design and optimisation of bioabsorbable magnesium devices for load-bearing medical applications.
