Carbon-based magnetic nanocarrier for controlled drug release: a green synthesis approach

In this study, hydrophilic magnetic nanoparticles were synthesized by green routes using a methanolic extract of Rubus ulmifolius Schott flowers. The prepared magnetic nanoparticles were coated with carbon-based shell for drug delivery application. The nanocomposites were further chemically functionalized with nitric acid and, sequentially, with Pluronic® F68 (CMNPs-plur) to enhance their colloidal stability. The resulting material was dispersed in phosphate buffer solution at pH 7.4 to study the Doxorubicin loading. After shaking for 48 h, 99.13% of the drug was loaded by the nanocomposites. Subsequently, the drug release was studied in different working phosphate buffer solutions (i.e., PB pH 4.5, pH 6.0 and pH 7.4) to determine the efficiency of the synthesized material for drug delivery as pH-dependent drug nanocarrier. The results have shown a drug release quantity 18% higher in mimicking tumor environment than in the physiological one. Therefore, this study demonstrates the ability of CMNPs-plur to release a drug with pH dependence, which could be used in the future for the treatment of cancer "in situ" by means of controlled drug release.This research was funded by: Project POCI-01-0145-FEDER-006984 – Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020 - POCI – and by national funds through FCT (Fundação para a Ciência e a Tecnologia); RTChip4Theranostics, supported by Programa Operacional Regional do Norte—Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by FCT. The authors are grateful to FCT, and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2013) and L. Barros contract. R.O.R. acknowledges the Ph.D. scholarship SFRH/BD/97658/2013 granted by FCT. This work was also supported by the Slovak Scientific Grant Agency projects VEGA 2/033/19.info:eu-repo/semantics/publishedVersio

Attenuation of the insulin amyloid aggregation in presence of Fe3O4-based magnetic fluids

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Combined Therapy with Simvastatin- and Coenzyme-Q10-Loaded Nanoparticles Upregulates the Akt-eNOS Pathway in Experimental Metabolic Syndrome

In addition to their LDL-cholesterol-lowering effect, statins have pleiotropic beneficial effects on the cardiovascular system. However, long-term treatment with statins may be associated with serious side effects. With the aim to make statin therapy more effective, we studied the effects of simvastatin- and coenzyme-Q10-loaded polymeric nanoparticles on the lipid profile and nitric oxide (NO)/reactive oxygen species (ROS) balance in the heart and aorta of adult male obese Zucker rats. The rats were divided into an untreated group, a group treated with empty nanoparticles, and groups treated with simvastatin-, coenzyme Q10 (CoQ10)-, or a combination of simvastatin- and CoQ10-loaded nanoparticles (SIMV+CoQ10). After 6 weeks, the lipid profile in the plasma and the concentration of conjugated dienes in the liver were determined. Nitric oxide synthase (NOS) activity, Akt, endothelial NOS (eNOS), phosphorylated eNOS (p-eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and nuclear factor kappaB (NF-kappaB) protein expressions were measured in the heart and aorta. All simvastatin, CoQ10, and SIMV+CoQ10 treatments decreased plasma LDL levels, but only the combined SIMV+CoQ10 treatment increased NOS activity and the expression of Akt, eNOS, and p-eNOS in both the heart and the aorta. Interestingly, NADPH oxidase in the heart and NF-kappaB protein expression in the aorta were decreased by all treatments, including nanoparticles alone. In conclusion, only combined therapy with SIMV- and CoQ10-loaded nanoparticles increased NOS activity and upregulated the Akt-eNOS pathway in obese Zucker rats, which may represent a promising tool for the treatment of cardiometabolic diseases

Development of Positively Charged Poly-L-Lysine Magnetic Nanoparticles as Potential MRI Contrast Agent

A colloidal solution of magnetic nanoparticles (MNPs) modified with biocompatible positively charged poly-L-lysine (PLL) with an oleate (OL) layer employed as an initial coating was produced as a potential MRI contrast agent. The effect of various PLL/MNPs’ mass ratios on the samples’ hydrodynamic diameter, zeta potential, and isoelectric point (IEP) was studied by the dynamic light-scattering method. The optimal mass ratio for MNPs’ surface coating was 0.5 (sample PLL0.5-OL-MNPs). The average hydrodynamic particle size in the sample of PLL0.5-OL-MNPs was 124.4 ± 1.4 nm, and in the PLL-unmodified nanoparticles, it was 60.9 ± 0.2 nm, indicating that the OL-MNPs’ surface became covered by PLL. Next, the typical characteristics of the superparamagnetic behavior were observed in all samples. In addition, the decrease in saturation magnetizations from 66.9 Am2/kg for MNPs to 35.9 and 31.6 Am2/kg for sample OL-MNPs and PLL0.5-OL-MNPs also confirmed successful PLL adsorption. Moreover, we show that both OL-MNPs and PLL0.5-OL-MNPs exhibit excellent MRI relaxivity properties and a very high r2(*)/r1 ratio, which is very desirable in biomedical applications with required MRI contrast enhancement. The PLL coating itself appears to be the crucial factor in enhancing the relaxivity of MNPs in MRI relaxometry

Effect of magnetic nanoparticles coating on cell proliferation and uptake

Magnetic iron oxide nanoparticles (MNPs) are one of the most promising types of nanoparticles for biomedical applications, primarily in the context of nanomedicine-based diagnostics and therapy. They are used as contrast agents in magnetic resonance imaging and magnetite cell labelling. Furthermore, they are promising heating mediator in magnetic hyperthermia-based therapy, and can serve as nanocarriers in targeted gene and drug delivery as well. In biomedical applications, coating plays an important role in nanoparticle dispersion stability and biocompatibility. However, the impact of nanoparticle surface chemistry on cell uptake and proliferation has not been sufficiently investigated. The objective of this study is to prepare magnetic nanoparticles with inner magnetite core and hydrophilic outer shell of surfactant, protein and polymers that are commonly used in biomedical research. MNPs were characterized in-depth by various physicochemical methods. Magnetic hyperthermia, applied to find out the influence of MNPs coating on heating characteristics of the samples, did not show any correlation between layer thickness and specific adsorption rate. To evaluate the impact of surface chemistry on cell proliferation and internalization, the human lung adenocarcinoma epithelial (A549) cells were utilized. Substantial differences were determined in the amount of internalized MNPs and cell viability in dependence on surface coating. Our results indicate that the surface chemistry not only protects particles from agglomeration but also affect the interaction between cell and MNPs. © 2018 Elsevier B.V

Design and preparation of proline, tryptophan and poly-l-lysine functionalized magnetic nanoparticles and their radiolabeling with 131I and 177Lu for potential theranostic use

Surface modification of magnetic nanoparticles with poly-L-lysine, proline, and tryptophan was used to design potential theranostic agents for the application in cancer diagnosis and radionuclide-hyperthermia therapy. Characterization of bare and functionalized magnetic nanoparticles was performed in detail. The transparency of the examined magnetic nanoparticles was measured in the non-alternating magnetic field for a complete and better understanding of hyperthermia. For the first time amino acid-functionalized magnetic nanoparticles were labeled with theranostic radionuclides 131I and 177Lu. The specific absorption rate (SAR) procured for poly-L-lysine functionalized magnetic nanoparticles (SAR values of 99.7 W/g at H0 = 15.9 kA/m and resonant frequency of 252 kHz) demonstrated their possible application in magnetic hyperthermia. Poly-L-lysine functionalized magnetic nanoparticles labeled with 177Lu showed the highest radiochemical purity (>99.00 %) and in vitro stability in saline and serum (>98.00 % up to 96 h). The in vivo analysis performed after their intravenous administration in healthy Wistar rats presented good in vivo stability for several days. Encouraging results as well as magnetic and radiochemical properties of 177Lu–PLL-MNPs (80 °C) justify their further testing toward the potential use as theranostic agents for diagnostic and combined radionuclide-hyperthermia therapeutic applications