Synthesis,Self-assembly And Controlled Drug Release Study Of Charge-reversal Coumarin-based Responsive Copolymer

Stimuli-responsive polymer is a kind of special polymer with stimulant groups,which can adjust its structure according to the external stimuli.Coumarin is a reversible photo-responsive group under the UV-irradiation.Thus,the coumarin is introduced into the polymer system with other stimulus to control the properties of the self-assembly system.PDMAEMA is a weak base with a pKb of 7.4,It is water-soluble below pH 7.4,and water-insoluble in strong alkaline environment.PAA is a weak acid with a pKa of 4.5,it can receive protons in acid solution,and release protons at neutral and high basic solution.Thus,they are applied widely to the stimuli-responsive polymer system.In this paper,RAFT is used to carry out the copolymerization of 7-(4-vinyl-benzyloxyl)-4-methylcoumarin(VBMC),DMAEMA and tBA by two steps,then we obtain the coumarin-based stimuli-responsive targetting block copolymerization P(VBMC-co-AA)-b-P(DMAEMA-co-St)by selective hydrolysis.In addition,we study the self-assembly behavior and drug controlled-release properties in the water solution for copolymer.The specific research contents for this paper is as fllows:1.RAFT was used to to carry out the random copolymerization of VBMC and tert butyl acrylate(tBA)to obtain a series of random copolymer P(VBMC-co-tBA)with different molar ratios.Then,P(VBMC-co-tBA)was used as a macro-molecule chain transfer agent to prepare the random copolymerization of PDMAEMA and PSt.Finally,the product is selective hydrolyzed by excessive TFA to obtain the coumarin-based stimuli-responsive targetting block copolymerization P(VBMC-co-AA)-b-P(DMAEMA-co-St).2.Self-assembly method in solution was used to prepare core-shell structure micelles,and the assembly behavior of micelles under UV and pH dual interaction was also studied.The research found that:In an aqueous solution with pH?4.0,the cationic micelles were formed due to the fully protonated PDMAEMA.At a pH rang of 5.0-7.8,the mixed core-shell structure micelles were formed due to the partially ionizated PAA and protonated PDMAEMA.In a pH range of 8.0-10.0,a large amount of precipitation was produced within the isoelectric point(IEP)region because of the electrostatic interaction between aggregates.In an aqueous solution with pH?10.0,the anionic micelles were formed with PAA blocks as the hydrophilic shell based on fully ionized PAA blocks.From pH 2 to pH 12,the particle sizes of the micelles increased first,then decreased.The Zeta potential showed that the particle sizes changed from +19.44 mV in strong acid solution to-27.88 mV in strong alkali solution.3.UV was used to study the photo-responsive of micelles.It was found that the UV absorption of micelles decreased obviously at 320 nm after 365 nm UV light irradiated.When the irradiated micelles were again irradiated after 254 nm UV light irradiated,the UV absorption slowly recovered,indicating that the photo-induced effect was reversible.4.DOX was used as the hydrophobic drug molecule to explore the drug release behaviors of DOX-loded micelles in vivo under pH and light dual interaction.MTT assay showed that DOX-loaded polymer micelles incubated with HeLa cells for 24 h owned a high viability(?80%).The cellular uptake test showed that DOX-loaded micelles entered the cells by slow endocytosis and released drug slowly in the cellular nuclei.Throught the drug release test in vitro of DOX-loaded micelles in different pH buffer solution,we found that there was an high accumulation release of DOX in the buffer solution of pH 4 and pH 9.18,and tend to steady after 42 h.However,the accumulation release of DOX was obviously reduced after photo-crosslinking,which proved that the photo-dimerization of coumarin had an inhibition effect on drug release behaviors of DOX-loded micelles with pH change.5.UV was used to study the aggregation induced emission(AIE)properties of P(VBMC-co-AA)-b-P(DMAEMA-co-St)in THF and in aqueous solution.It was found that the fluorescence intensity of coumarin moleculars decreased gradually from pH 2 to pH 6,again increased to pH 12,and reached the minimum value in THF.