Acrylates-based hydrophilic co-polymeric nanobeads as nanocarriers for imaging agents

Abstract

Acrylates-based co-polymeric nanoparticles (PNPs) are widely used in nanomedicine applications due to their tunable hydrophilic surface, physical and chemical versatility. Particularly attracting is their use as nanocarriers for imaging agents. Herein, methyl methacrylate (MMA) and N,N-dimethylacrylamide (DMAA) monomers were used to synthesize hydrophilic p(MMA-co-DMAA) nanoparticles in the 200–600 nm size range via surfactant-free radical emulsion polymerization technique. Different MMA/DMAA molar ratios, temperatures, and reaction times were investigated to evaluate their role in determining the average particle size, polydispersity, and optimizing surface properties of PNPs. Nanoparticles formation, stability (in water and culture medium for cell growth), swelling behavior, structural features and molecular weights were assessed by spectroscopic, non-spectroscopic, and chromatographic techniques. Morphological profiles confirming spherical-shaped NPs were obtained at solid state via microscopies (FESEM, AFM). To use such colloids as potential imaging agents, PNPs were loaded with Y3+(aq) ions by the addition of aqueous solutions of YCl3 at different concentrations, and results compared with p(MMA-co-AA)-DTPA NPs (AA = acrylic acid) functionalized with DTPA chelating agent. Yttrium ions loading percentage was ca. 90% for both p(MMA-co-DMAA) and p(MMA-co-AA)-DTPA, with negligible release (<15%) over a month. Parallelly, optical imaging nanoprobes were obtained by physical encapsulation of fluorescein isothiocyanate isomer I (FITC) dye during the synthesis process, and the spontaneous FITC incorporation was evaluated by spectroscopic studies and fluorescence microscopy. Cytotoxicity studies on pristine and yttrium-loaded nanoparticles were done in vitro on human glioblastoma T98G cell line within 24 h of treatment. Transmission electron microscopy (TEM) studies on cancer cells treated with NPs confirmed an active uptake of PNPs through multiple endocytic pathways to reach the perinuclear region of the cell. Overall, this work elucidated the role of synthetic parameters for a rational design of hydrophilic PNPs as nanocarriers for imaging agents with potential applications in theranostics.