Synthesis And Applications Of Multi-functional Hyperbranched Poly(Amido Amine)s

Hyperbranched polymers have attracted much attention due to their unique physical and chemical properties, show potential applications in supramolecular chemistry, drug delivery, gene therapy and bioimaging. In the last decade, remarkable achievements have been made in the synthesis, characterization, modification and applications of hyperbranched polymers. Currently, develop multi-functional hyperbranched polymers, explore their unknown feature and spread the application fields have become more important. In this dissertation, we have synthesized some multi-functional hyperbranched poly(amido amine)s through using well-desigened functional monomers, and researched their applications in self-assembly and gene delivery. The details and key conclusions are described as follows:1. A novel disulfide-containing hyperbranched poly(amido amine) was prepared by Michael addition of N,N’-cystaminebisacrylamide and N,N’-methylenebisacrylamide with1-(2-aminoethyl)piperazine. The synthesized hyperbranched poly(amido amine) is multi-functional, such as stimuli-responsiveness, good water-solubility, biocompatibility, excellent buffer capacity and strong photoluminescence. It was interesting to find that hyperbranched poly(amido amine) can easily assemble plasmid DNA into nanorings, while the similar linear poly(amido amine) only can assemble plasmid DNA into nanoparticles. This mainly benefit from the topology structure of the hyperbranched polymer. The structure of formed nanorings and the presumed mechanism were characterized and proved by AFM. These fabricated nanorings are not only photoluminescent but also stimuli-responsive and biocompatible, which will have potential applications in gene and drug delivery and molecular imaging.2. The disulfide-containing hyperbranched poly(amido amine)s prepared by Michael addition of N,N’-cystaminebisacrylamide with1-(2-aminoethyl)piperazine is easily self-crosslinking through intermolecular disulfide exchanges. Further investigations show that the intermolecular disulfide exchanges of disulfide-containing hyperbranched poly(amidoamine)s occur easily in the solid state or in solution at high concentration. We further introduce N,N’-dimethylamine into the disulfide-containing hyperbranched poly(amido amine)s via Michael addition polymerization of N.N’-cystamine bisacrylamide with N,N’-dimethyldipropylenetriamine. N,N’-Dimethylamine can hydrate at low temperature in aqueous solution, but easily dehydrates at high temperature, which leads this disulfide-containing hyperbranched poly(amido amine)s to temperature-responsive. Thus though heating the polymer solution temperature above the lower critical solution temperature, polymers firstly assemble into nanoparticles, and then the disulfide bonds are in a very compact environment inside such nanoparticles which can undergo intermolecular disulfide exchange, crosslinking the nanoparticles/microparticles to form nanogels/microgels. The size of formed nanogels/microgels can be tuned via the polymer concentration, and the formed nanoparticles are biocompatible and bioreducible.3. A novel glycopolymer with a hyperbranched poly(amido amine) core and a sugar shell (HPAA-GLc) was synthesized by using thiol-ene click reaction via facile one-pot method. Hyperbranched poly(amido amine) with vinyl terminals was first synthesized by Michael addition polymerization of N,N’-methylene bisacrylamide (MBA) with1-(2-aminoethyl) piperazine (AEPZ). Subsequently, thiol-ene click reaction between vinyl units of hyperbranched poly(amido amine) and thio-glucose was performed in situ. Based on the NMR result, all the vinyl groups reacted with thiol-glucose in120min. Strong photoluminescence emission was observed from the aqueous solution of HPAA-GLc.4. Poly(amido amine)s with both bioreducible and acid-labile properties were synthesized by Michael addition reaction for gene delivery. It was found that the presence of acid-labile units in polymers can facilitate endosomal escape and that the presence of reducible units in polymers can lead to intracellular release. The complexes of DNA with dual-responsive polymers showed higher gene transfection efficiency than single-responsive polymers. At the same time, these polymers were less cytotoxic, represent an innovative approach for efficient and biocompatible gene delivery.