ABSTRACT
The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against â¢DPPH, â¢OH and O2â¢-, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 µg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.
Subject(s)
Drug Delivery Systems , Folic Acid , Fullerenes , Povidone , Folic Acid/chemistry , Folic Acid/pharmacology , Humans , Povidone/chemistry , Fullerenes/chemistry , Fullerenes/pharmacology , Drug Delivery Systems/methods , Cell Line, Tumor , A549 Cells , HeLa Cells , Particle SizeABSTRACT
Huntington's disease (HD) is one of the human neurodegenerative diseases for which there is no effective treatment. Therefore, there is a strong demand for a novel neuroprotective agent that can alleviate its course. Fullerene derivatives are considered to be such agents; however, they need to be comprehensively investigated in model organisms. In this work, neuroprotective activity of C60(OH)30 and C120O(OH)44 fullerenols was analyzed for the first time in a Drosophila transgenic model of HD. Lifespan, behavior, oxidative stress level and age-related neurodegeneration were assessed in flies with the pathogenic Huntingtin protein expression in nerve cells. Feed supplementation with hydroxylated C60 fullerene and C120O dimer oxide molecules was shown to diminish the oxidative stress level and neurodegenerative processes in the flies' brains. Thus, fullerenes displayed neuroprotective activity in this model.
Subject(s)
Fullerenes , Huntington Disease , Animals , Humans , Drosophila , Huntington Disease/drug therapy , Huntington Disease/genetics , Huntington Disease/metabolism , Fullerenes/pharmacology , Oxidative Stress , Neurons/metabolismABSTRACT
Application of dilational surface rheology, surface tensiometry, ellipsometry, Brewster angle, and transmission electron and atomic force microscopies allowed the estimation of the structure of the adsorption layer of a fullerenol with a large number of hydroxyl groups, C60(OH) X ( X = 30 ± 2). The surface properties of fullerenol solutions proved to be similar to the properties of dispersions of solid nanoparticles and differ from those of the solutions of conventional surfactants and amphiphilic macromolecules. Although the surface activity of fullerenol is not high, it forms adsorption layers of high surface elasticity up to 170 mN/m. The layer consists of small interconnected surface aggregates with the thickness corresponding to two-three layers of fullerenol molecules. The aggregates are not adsorbed from the bulk phase but formed at the interface. The adsorption kinetics is controlled by an electrostatic adsorption barrier at the interface.
