Bimodal Fucoidan-Coated Zinc Oxide/Iron Oxide-Based Nanoparticles for the Imaging of Atherothrombosis

Abstract

A polyol method was used to obtain ultrasmall ZnO nanoparticles (NPs) doped with iron ions and coated with a low molecular weight fucoidan in order to perform in vivo MR and ex vivo fluorescence imaging of athrothrombosis. During the synthesis, the early elimination of water by azeotropic distillation with toluene allowed us to produce NPs which size, determined by XRD and TEM, decreased from 7 nm to 4 nm with the increase of iron/zinc ratios from 0.05 to 0.50 respectively. For the highest iron content (NP-0.50) NPs were evidenced as a mixture of nanocrystals made of wurtzite and cubic phase with a molar ratio of 2.57:1, although it was not possible to distinguish one from the other by TEM. NP-0.50 were superparamagnetic and exhibited a large emission spectrum at 470 nm when excited at 370 nm. After surface functionalization of NP-0.50 with fucoidan (fuco-0.50), the hydrodynamic size in the physiological medium was 162.0 ± 0.4 nm, with a corresponding negative zeta potential of −48.7 ± 0.4 mV, respectively. The coating was evidenced by FT-IR spectra and thermogravimetric analysis. Aqueous suspensions of fuco-0.50 revealed high transverse proton relaxivities (T2) with an r2 value of 173.5 mM−1 s−1 (300 K, 7.0 T) and remained stable for more than 3 months in water or in phosphate buffer saline without evolution of the hydrodynamic size and size distribution. No cytotoxic effect was observed on human endothelial cells up to 48 h with these NPs at a dose of 0.1 mg/mL. After injection into a rat model of atherothrombosis, MR imaging allowed the localization of diseased areas and the subsequent fluorescence imaging of thrombus on tissue slices.

Evaluation of MxOy/fucoidan hybrid system and their application in lipase immobilization process

“…Due to its unique features, fucoidan is a promising biopolymer that can also be utilized as a coating material. To date, fucoidan-modified materials have been used in medical applications such as drug delivery 48 – 52 . The magnetic mesoporous silica system was modified with fucoidan by Moorthy et al 48 .…”

Targeting P-Selectin Adhesion Molecule in Molecular Imaging: P-Selectin Expression as a Valuable Imaging Biomarker of Inflammation in Cardiovascular Disease

“…A recent publication also reported on an MRI approach for imaging atherothrombosis in a aneurysmal thrombosis rat model using fucoidan-coated ultrasmall superparamagnetic and luminescent Zn(Fe)O hybrid nanoparticles. These nanoparticles contain an iron-to-zinc ratio of 0.50, which offers bimodal versatility for both MRI and optical imaging capabilities (28). The study by Nguyen et al showed increased MRI signal within 30-60 min of nanoparticle injection in a rat with a confirmed small thrombus, with the maximum signal reached after 2 h. MRI of injected nanoparticles identified diseased tissue, which was then harvested and imaged with an optical microscope to assess nanoparticle luminescence.…”

“…The study by Nguyen et al showed increased MRI signal within 30-60 min of nanoparticle injection in a rat with a confirmed small thrombus, with the maximum signal reached after 2 h. MRI of injected nanoparticles identified diseased tissue, which was then harvested and imaged with an optical microscope to assess nanoparticle luminescence. Although there was large optical imaging autofluorescence associated with the collagen in the vessel wall, bright regions in the thrombus could represent high amounts of the P-selectin-targeted nanoparticles (28).…”

A Review of Microwave Synthesis of Zinc Oxide Nanomaterials: Reactants, Process Parameters and Morphologies

“…It has been proved that ZnO NPs applied in textiles effectively fight bacteria, e.g., Staphylococcus aureus or Klebsiella pneumoniae [ 182 ]. In medicine, research is in progress on the application of ZnO NMs as a potential contrast agent (imaging), drug carrier, iron delivery, gene carrier, biosensor, a potential anti-cancer agent, in a photodynamic therapy, for prophylactic and therapeutic vaccines, support for antifungal treatments, in photocatalytic antibiotics, inhibition of influenza virus infection, diagnostic-therapeutic functions, wound dressing and tissue engineering [ 70 , 166 , 168 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 ]. However, before implementing ZnO NMs in biomedical applications on a commercial scale, the toxicity of ZnO NMs must be carefully learnt and their toxicity mechanisms must be explained [ 121 , 162 , 171 , 174 , 178 , ...…”