Stimuli-responsive Polymer Nanohydrogels For Biomedical Applications

Due to their good biocompatibility and high specific surface area,the stimuli-responsive polymer nanohydrogels have been widely employed as drug nanocarriers with high drug load capacity and controlled drug release abilities.However,the synthesis process of the polymer nanohydrogels is quite complicated and some of the prepared nanohydrogels are monofunctional.Herein,a variety of multifunctional stimuli-responsive polymer nanohydrogels were fabricated by the facile reflux-precipitation polymerization method.The polymer nanohydrogels were furthermore employed as excellent drug nanocarriers with multifunctionalities for cancer therapy.?1?A series of stimuli-responsive polymer nanohydrogels were synthesized by the reflux-precipitation polymerization using hydrophilic monomers,hydrophobic monomers,cationic monomers and amphiphilic monomers with different crosslinkers.The poly?acrylic acid-co-3-methacrylamide dopamine?nanohydrogels?poly?AA-co-DMA?NG?was synthesized using acrylic acid and 3-methacrylamide dopamine as monomers.As the amount of monomers,cross-linkers and initiators increased,the size of polymer nanohydrogel increased,indicating the important effect of experimental conditions on the nanohydrogel synthesis.?2?Based on the versatility of catechol functional groups in DMA,the poly?AA-co-DMA?nanohydrogel with pH/redox double stimuli-responses were employed as a universal platform for conjugation with Fe₃O₄ nanoparticles and drug bortezomib?BTZ?.The Fe₃O₄ nanoparticles decorated poly?AA-co-DMA?nanohydrogels?Fe₃O₄@NG?can be utilized as nanocarriers for doxorubicin?DOX?with the drug releasing efficiency of 80.3%.Under the external magnetic field,the DOX-Fe₃O₄@NG delivery system exhibited good targeting abilities and antitumor efficacy.As for the dual drug delivery system,the DOX-BTZ@NG showed higher antiproliferation efficacy to cancer cells in comparison with the single drug loaded nanohydrogels,suggesting a synergistic effect of the dual drug combination therapy with the the CI₅₀ index of 0.32.The stimuli-responsive poly?AA-co-DMA?nanohydrogels with surface-tailorable functionalities are thus a promising versatile platform for conjugation with both nanomaterials and drug molecules.?3?The poly?AA-co-NIPAAm?nanohydrogels with pH/redox/temperature triple stimuli-responses were prepared by the reflux-precipitation polymerization.Combined with the photothermal conversion and photoacoustic imaging properties of aniline tetramer?AT?,the DOX-AT@NG system were developed for the image-guided chemo-thermo cancer therapy.Under the stimuli of pH 5.0/GSH/NIR,the drug can be effectively released.Furthermore,the DOX-AT@NG system exhibited strong photoacoustic signals and excellent photothermal conversion properties.Under near-infrared light irradiation,the tumor cells were greatly reduced to9.7%by using the DOX-AT@NG drug delivery system,indicating the improved treatment efficacy of the synergistic chemo-thermo therapy.