Synthesis And Application Of Stimuli-Responsive Polymers With Oxime Linkages

Dynamic polymers have become one of the highlights in the field ofsmart materials because of their extraordinary environmental adaptabilityand stimuli responsiveness. In order to improve the environmentaladaptability, enhance the sensitivity and create programmable releasebehavior, various dynamic bonds have been introduced into differentpolymeric backbones, such as disulfide bond, imine bond andacylhydrazone bond. As a member of dynamic library, oxime bond hasbeen constructed into different polymeric research because of their facilesynthetic method, high environmental adaptability and acute sensitivity.Based on our group’s traditional advantages in the research areas ofbiomedical materials and hyperbranched polymers, two oxime-tetheredstimuli-responsive linear and hyperbranched polymeric systems havebeen designed and synthesized in the present work. Specifically, twoaspects have been studied: one is pH responsiveness and release hehaviorof the oxime-contained linear polymeric delivery system; the other is stimuli-responsive self-assembling behavior of nonamphiphilichyperbranched polyoximes.(1) We confirmed that oxime linkage was a robust tool for the design ofpH-sensitive polymeric drug delivery systems. The triblock copolymer(PEG-OPCL-PEG) consisting of hydrophilic poly(ethylene glycol)(PEG)and hydrophobic oxime-tethered polycaprolactone (OPCL) wassuccessfully prepared by aminooxy terminals of OPCL condensating withaldehyde-terminated PEG (PEG-CHO). As a drug carrier, the propertiesof this amphiphilic dynamic PEG-OPCL-PEG were different from thoseof traditional PEG-PCL-PEG tethered with amido and ester linkages.First of all, the intermolecular interaction could be generated between thecarbanyl groups of the anticancer drug doxorubicin and the oxime bondsof PEG-OPCL-PEG, thus improving the drug loading efficiency of thewhole drug delivery system. Furthermore, polymeric drug deliverysystem containing oxime bonds could be transported to the endosome orlysosome of tumor cells, and the encapsulated anticancer DOX could begradually released through the degradation of pH-sensitive oxime bonds.The hydrophobic/hydrophilic ratio, the drug loading efficiency, pHsensitivity and degradability could be adjusted with the variation of theoxime content.(2) We realized the self-assembly of nonamphiphilic hyperbranched polymer. Hyperbranched polyoximes (HPOXs) were successfullysynthesized by the polycondensation of trialdehyde and bis-aminooxymonomers through A2+B3polymerization method, and it could be foundthat HPOXs possessed very unique self-assembly behaviors. Withoutamphiphilic block segments, HPOXs with a torispherical structure couldself-assemble into the homogeneous and well-dispersed nanoparticles in amixed solution of dimethyl sulfoxide and H2O. With the help of nuclearmagnetic resonance (NMR), Fourier transform infrared spectroscopy(FT-IR), scanning electron microscopy (SEM), transmission electronmicroscopy (TEM), atomic force microscopy (AFM) and fluorescencespectroscopy (FL), it was found that the oxime bonds, aminooxyterminals and amide bonds of HPOXs formed the intra-andinter-molecular noncovalent interaction, leading to the formation of theHPOX nanoparticles. The modulation of the degree of branching (DB)and the terminal groups resulted in different sizes and morphologies dueto the change of the intra-and inter-molecular interactions. Dynamicoxime linkages and hydrogen bonds endowed HPOXs and theirnanoparticles with pH and thermal dual responsiveness, which wasconducive to further studying the tentative self-assembly mechanism.Furthermore, the self-assemblies of HPOXs will render us with aprofound understanding of the sophisticated self-assembling behavior of nonamphiphilic biomolecules.