A novel polysaccharide-based zwitterionic copolymer, agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (agarose-g-PDMAPS) with UCST, depending both on hydrogen bonding and electrostatic interaction, was synthesized by ATRP, and its aggregation behavior in aqueous media was investigated in detail. Proton nuclear magnetic resonance spectroscopy, Fourier transform-infrared spectroscopy, and gel-permeation chromatography were performed to characterize the copolymer. Thermosensitive behaviors of the copolymers in water, NaCl, and urea solution were tracked by ultraviolet, dynamic light scattering, and transmission electron microscopy analysis. It was found that the copolymers existed as "core-shell" spheres at an elevated temperature, as a result of the self-assembly of the agarose backbones located in the "core" driven by hydrogen-bonding interactions. When the copolymer solution was cooled below UCST, the core-shell spheres began to aggregate because of the electrostatic interactions and collapse of PDMAPS side chains in the "shell" layer. UCST of the copolymer could be tuned in a wide range, depending on the chain lengths of PDMAPS. This is the first example to investigate the thermosensitivity, combining ionic interactions of the zwitterionic side chains with hydrogen bondings from the biocompatible agarose backbones. The synthetic strategy presented here can be employed in the preparation of other novel biomaterials from a variety of polysaccharides.
Multifunctional drug carriers have great applications in biomedical field. In this study, we introduced both polydopamine (PDA) and zwitterionic polymer of poly(3-(3-methacrylamidopropyl-(dimethyl)-ammonio)propane-1-sulfonate) (PSPP) onto the surface of mesoporous silica nanoparticles (MSNs) to develop a novel nanoparticle (MSNs@PDA-PSPP), which was employed as a new kind of drug carrier for the delivery of doxorubicin (DOX). The PDA coating, as a gatekeeper, could endow the drug carrier with pH-sensitive drug release performance. The outermost PSPP layer would make the drug carrier possess protein resistance performance. The chemical structure and properties were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). MSNs@PDA-PSPP could keep good colloidal stability within 72 h in phosphate buffered saline (PBS) and protein solutions. Meanwhile, MSNs@PDA-PSPP exhibited a high drug loading for DOX. In vitro drug release experiments suggested MSNs-DOX@PDA-PSPP exhibited pH-dependent drug release behaviors. Besides, MSNs@PDA-PSPP had no cytotoxicity to human hepatocellular carcinoma cells (HepG2 cells) even at a concentration of 125 µg/mL. More importantly, cellular uptake and in vitro anticancer activity tests suggested that MSNs-DOX@PDA-PSPP could be taken up by HepG2 cells and DOX could be successfully released and delivered into the cell nuclei. Taken together, MSNs@PDA-PSPP have great potential in the biomedical field.
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