Research On Synthesis Technology Of Novel Nano Bottlebrush Polymer Based On Hyperbranched Polymer Side Chain

Bottlebrush copolymers are broadly explored as nano drug carrying materials.However,current bottlebrush copolymers are mostly synthesized with polyolefins,such as polystyrenes and polyacrylates as the side chain.These polymers with carbon backbones usually have poor biocompatibility.We have developed a new synthetic pathway to prepare hyperbranched polyglycerols as the side chains of a nano bottlebrush copolymer.The numerous hydroxyl groups on the polyglycerol can couple with a variety of drugs and tumor targeting ligands,making this bottlebrush copolymer a promising nano drug carrier.First,a new synthetic method of-NH₂ terminated hyperbranched polyglycerol was developed.Using O-（2-aminoethyl）polyethylene glycol（NH₂-PEG-OH）as the substrate,hydroxyl-end-initiated glycidyl ring opening polymerization（h PG）was conducted after protection of the-NH₂ group by triphenylmethyl chloride.The triphenylmethyl moieties were then detached by acetic acid and the-NH₂ group was recovered.We synthesized a new hyperbranched polymer（NH₂-PEG-h PG）with amino group at one end and polyhydroxy group at the other end.The asymmetric functionalization of hyperbranched polymers was realized.The polymerization purification process was also optimized.The molecular weight of the synthesized NH₂-PEG-h PG was controlled within the range of 3000～9740 g/mol,and the polydispersity index PDI was below 1.17.Subsequently,using above-mentioned different molecular weight of hyperbranched polymer NH₂-PEG-h PG as the starting material,novel macromonomer Norb-PEG-h PG（The molecular weight was in the range of3250～4660 g/mol,PDI was below 1.1）was synthesized from its terminal amino group and norbornene derivative via amidation reaction;paclitaxel was successfully linked to Norb-PEG-h PG to produce drug loaded macromonomer Norb-PEG-h PG-SA-PTX.The cytotoxicity and drug activity were investigated via MTT method,and the drug-loaded Norb-PEG-h PG-SA-PTX polymers was founded against cancer cells.Finally,utilizing the above macromonomer Norb-PEG-h PG,a novel nano bottlebrush polymer Brush-PEG-h PG with hyperbranched polyglycerol as side chain was synthesized by Ring-Opening Metathesis Polymerization（ROMP）;the effects of the catalyst and solvent on romp reaction and polymer molecular weight were studied.The results showed that when N,N-dimethylformamide was selected as solvent and the molar ratio of catalyst and macromolecular monomer was 1:20,nano bottlebrush polymer with maximum molecular weight of 93200 g/mol and polymerization degree 20 was synthesized.The PDI was1.19,the diameter of the polymer was 20～40 nm and the length was 40～60 nm.