Bioinspired Materials Prepared Via Ring Opening Reaction Of Phospholane For Nanodrug And Bio-Hydrogel Applications

Recently,with the great development of bioscience and materials chemistry,the biomaterials have enabled many applications in modern medicine from the disease diagnosis and treatment to artificial organs replacement.The "living biomaterials"has been paid more and more attention and made great progress since it's first proposed as the next generation biomaterials several years ago.The"living biomaterials"could effectively sense the subtle changes so that to make rapid responses for the biological systems.For example,the remote-controlled microchipsdrug delivery system and artificial tissues have been successfully applied to clinic.The phospholane is one of the most important monomer for organophosphorous materials,which is easily prepared and abundant.What's more,these organophosphorous materials prepared via ring-opening reactions are usually biocompatible,and have been widely applied in various biomedical field.Herein,we have designed and prepared serials materials via ring-opening reactions in the presence of phospholane monomer and various initiators for theapplications in nano drug delivery system and tissue engineering.The main contents and conclusions are summarized as follows:Firstly,the cell membrane inspired choline phosphate(CP)monomer has been prepared in the presence of phospholane and initiator 2-(dimethylamino)ethyl methacrylate,and then polymerized to be block copolymers via atom transfer radical polymerization(ATRP).The anticancer drug Doxorubicin(Dox)was conjugated to the polymer chain via acid-labile hydrazone bond.All results demonstrated that this polymer prodrug can effectively adhere to the cell membrane via electronstatic interaction between the multivalent CP and PC group,and then was internalized to enhance the drug concentration in cells.After that,the hydrazone bond would be continuously cleaved at lysosome/endosome pH environment and the Dox could diffuse into nucleus to exert effect.Based on the previous works,we also prepared a novel polymer drug delivery system constructed with poly(choline phosphate)and poly(?-caprolactone)(PCL),which were linked by bioreducible disulfide bond.Interestingly,the excellent hydrophility of these zwitterionic CP groups endowed high drug loading content of Dox to this drug delivery system.In addition,we also demonstrated that the use of multivalent choline phosphate was conducive to enhance the delivery of Dox into the cancer cells,and the degree of improvement depended on the CP density in a single polymer chain.What' more,due to the different GSH concentration between extra-and intra-cellular compartments,this delivery system can effectively circumvent the premature release of drug and improve intracellular drug release in response to intracellular levels of glutathione to enhance therapeutic effect.The biodegradable polyphosphoester was prepared via ring opening polymerization in the presence of polyethylene glycol(PEG)and phospholane.Then,inspired from the multiple hydrogen bonds interactions of DNA,various acrylate nucleobase monomers were introduced into the polyphosphoester,and crosslinked with pendant groups via radical polymerization to construct three-dimensional network hydrogels.Interestingly,these hydrogels could effectively attach to various substrate surfaces,including silicon rubber,plastics,glass,polytetrafluoroethylene and fresh biological tissues.More importantly,these hydrogels exhibited controllable biodegradation behaviors and adhesion strength via controlling the nucleobase species and fractions,showed great potential in the applications of biomedical adhesives.