Construction Of Photo-Induced Hydrogen-Bonding Polymer Complexes And Application For Drug Periodic Release

Since the assembly of amphiphilic block polymers has great potential application value in the field of nano-drug carriers,research on self-assembly of amphiphilic block polymers has attracted much attention in recent years.Because the morphology of the amphiphilic block polymer assembly is diverse,such as spherical micelles,rod micelles,layered micelles,and double-layered vesicles,and the molecular structure of the block polymer can be designed flexibly,so drug-carriers constructed from amphiphilic block polymers are better able to accommodate the loading of diverse nanomedicines and the delivery in different physiological and pathological environments.At the same time,stimuli-responsive chemical groups can also be introduced into the polymer structure,thereby enabling the drug carrier constructed from the stimuli-responsive polymer to more easily control the release of the drug.However,the traditional block polymer assembly is mainly driven by physical effects such as hydrophobic interaction,and the structure of the drug carrier constructed by it is unstable,so that it is easy to cause the carrier structure to be destroyed when the drug carrier circulates in the living body.As a result,the drug in the load is leaked,the release efficiency of the drug is lowered,and the probability of side effects of the drug is increased.Therefore,how to solve the problem of improving the stability of drug carriers under the premise of ensuring drug release needs to be solved.In general,the stability of the assembly is improved by covalently crosslinking the polymer molecular chains in the assembly having stimuli responsiveness,but at the same time,the loading efficiency of the drug is greatly reduced.Recently,Professor Liu and others have invented a high mechanical strength,thermoplastic and self-healing polymer hydrogel in which the gel structure mainly depends on the poly?N-acryloyl glycinate?side chain on the dual-amide structure.This provides a new idea for the cross-linking of non-covalently bonded polymers to improve the stability of the assembly.Based on the above inspiration,this paper designed a photo-responsive monomer,N?-?2-nitrobenzyl?-N-acrylamide glycine amide?NBNAGA?,which contains a dual-amide structure that can produce double hydrogen and caged by 2-nitrobenzyl group.After the monomer and the RAFT chain transfer reagent having a poly?ethylene glycol?block are successfully polymerized by Reversible Addition-Fragmentation Chain Transfer Polymerization?RAFT?,the amphiphilic block copolymer,PEG₄₅-b-PNBNAGA_n,can be obtained.and self-assembled using the resulting amphiphilic block polymer,successfully formed a photo-responsive micelle assembly capable of supporting a hydrophobic drug.Then,the obtained amphiphilic block polymer was used for self-assembly,and a light-responsive micelle assembly capable of supporting a hydrophobic drug was successfully obtained.The assembly of loading the hydrophobic drug doxorubicin after the irradiation of365 nm ultraviolet light,the light-responsive group for the"cage"dual-amide structure in the polymer micelle core,2-nitrobenzyl group,will degradation and removal.The dual-amide structure on the side chain of the polymer is exposed,and the double hydrogen bond cross-linking between the polymer molecular chains is generated,thereby greatly improving the structural stability of the polymer micelle assembly.At the first stage,due to the photodissociation of the hydrophobic structure on the side chain of the polymer,the micelle core is transformed from the hydrophobic to the hydrophilic,and the permeability of the micelle assembly is increased,and further triggered the release of the first phase of the drug doxorubicin.Then,the assembly after ultraviolet light irradiation is heat-treated to destroy the double hydrogen bond cross-linking inside the assembly,and the whole structure of the assembly is completely collapsed and dissociated.Eventually,the complete release of the second phase of the drug-loaded drug doxorubicin was induced and achieved.