We present the synthesis and characterization of zwitterionic poly(4-vinylpyridine) nanoparticles modified with phenylboronic acid (QxPVP-PBA). We studied three different degrees of modification, which differed in both physicochemical and saccharide-sensing properties. The pKa values of QxPVP-PBA, determined by potentiometry and by 11B NMR spectroscopy, increased with the degree of PVP quaternization due to repulsion between charged groups. By dialysis of QxPVP-PBA polymers dissolved in HCl against MOPS buffer, we prepared stable nanoparticles at neutral pH, mostly stabilized by positive charges and by chains likely interconnected through cyclic PBA structures termed boroxines. QxPVP-PBA hydrophobicity increases with the decrease in the degree of PVP quaternization due to hydrophobic uncharged pyridine groups, as indicated by covalent binding to the PBA fluorescent probe alizarin. By potentiometric titrations and zeta potential measurements, we determined the pKa values of a fructose and glucose complex with the polymer, which were lower than the physiological pH. In addition, the alizarin displacement assay showed that QxPVP-PBA has a higher affinity to fructose than to glucose. Fructose binding leads to an increase in the size of the polymeric nanoparticles because their hydrophobicity increases after zwitterionic complex formation, as evaluated by LS and cryo-TEM. Notably, such fructose-bound particles showed a negative zeta potential. Therefore, QxPVP-PBA has unique charge reversal properties in the presence of saccharides.
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by the rapid onset of lung inflammation Therefore, monitoring the spatial distribution of the drug directly administered to heterogeneously damaged lungs is desirable. In this work, we focus on optimizing the drug N-acetylcysteine (NAC) adsorption on poly-l-lysine-modified magnetic nanoparticles (PLLMNPs) to monitor the drug spatial distribution in the lungs using magnetic resonance imaging (MRI) techniques. The physicochemical characterizations of the samples were conducted in terms of morphology, particle size distributions, surface charge, and magnetic properties followed by the thermogravimetric quantification of NAC coating and cytotoxicity experiments. The sample with the theoretical NAC loading concentration of 0.25 mg/mL was selected as an optimum due to the hydrodynamic nanoparticle size of 154 nm, the surface charge of +32 mV, good stability, and no cytotoxicity. Finally, MRI relaxometry confirmed the suitability of the sample to study the spatial distribution of the drug in vivo using MRI protocols. We showed the prevailing transverse relaxation with high transverse relaxivity values and a high r2(*)/r1 ratio, causing visible hypointensity in the final MRI signal. Furthermore, NAC adsorption significantly affects the relaxation properties of PLLMNPs, which can help monitor drug release in vitro/in vivo.
Engineered nanoflowers of gadolinium-doped maghemite (γ-Fe 2 O 3 ) offer a novel theranostic platform. Ultra-low Gd 3+ doping optimizes them for both magnetic resonance imaging (MRI) and magnetic hyperthermia.
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.