Dual-Responsive Shell Cross-Linked Micelle As Nanocarriers & Study Of 9-Anthranol Based Active Urethane

In the traditional cancer treatment,optical therapy has attracted much attention in recent years because of its good specificity and non-invasive treatment.In photodynamic therapy(PDT),a specific wavelength of light source is used to illuminate the vicinity of tumor tissue,and then photosensitizer absorbs photon energy under the stimulation of light and transfers the energy to oxygen atoms,thus producing a highly oxidizing singlet oxygen(1O2).This highly reactive oxygen species(ROS)can effectively oxidize biological macromolecules in cancer tissues and produce cytotoxinsdirectly,which lead to damage and apoptosis of cancer cells.Photothermal therapy(PTT)uses photothermal reagents to release energy through exothermic under the excitation of light,so as to achieve the purpose of cancer treatment.Compared with PDT,photothermal therapy is a kind of therapy without oxygen atoms,which is very suitable for cancer environment with extreme hypoxia.Recently,a novel optical therapy,photochemistry internalization(PCI),has been reported.Its basic principle is similar to that of PDT.It is a photoresponsivenanocarrier.Of course,the singlet oxygen produced by PCI is not mainly used in the treatment of PDT.It mainly destroys the nanocarrier membrane,dissociates it and releases all the chemotherapeutic drugs or genes loaded inside it,after which the targeted specific treatment of tumors can be achieved.In this paper,a pH-sensitive double hydrophilic block copolymer micelle was constructed using pH-sensitive poly(N,N'-diisopropylaminoethyl methacrylate)(PDPA)as hydrophobic block and oligoethylene glycol as hydrophilic block.Using the properties of photosensitizer PpIX fluorescence aggregation quenching,a photothermal effect is achieved in neutral environment,while photodynamic therapy and controlled drug release are demonstrated in weak acid environment1.A double hydrophilic block copolymer P(OEGMA.co-ABEMA)-b-P(DPA-co-PpIX)was synthesized by RAFT polymerization.P(DPA-co-PpIX)is a pH-responsive and covalently bonded segment with photosensitizerPpIX.Hydrophilic block P(OEGMA-co-ABEMA)is a segment obtained by copolymerization of oligoethylene glycol methacrylate and monomer with aldehyde functional unit(aldehyde functional unit for polymer assembly shell crosslinking,where the monomer is 4-formylphenyl oxyethyl methacrylate).The polymer was assembled into nanomicelles and then crosslinked by crosslinking agent 9,10-aminoethoxyanthracene(An.2NH2).Finally,the stability and pH sensitivity of shell-crosslinkednanomicelles were studied.In addition,the photodynamic effects and drug release ability of shell-crosslinkednanomicelles under light conditions were also tested.2.Two 9-Anthranolbased compounds,named ACB and ACMA,were synthesized.The tautomerism of carbamate group structure in ACBmolecule was studied.Pentafluorobenzoic acid(PFBA)was used as a hydrogen bond donor to influence the tautomerism balance of carbamate groups in ACB by hydrogen bonding between molecules.The experiment of the exchange reaction between the terminal group(9-Anthranol)of ACB molecule compound with benzylamine/benzyl alcohol under the condition of triethylamine(TEA)was also discussed.Finally,the copolymers with ACMA as monomer were obtained by RAFT polymerization.In view of the fact that small molecules can effectively exchange with benzylamine/benzyl alcohol under the condition of triethylamine(TEA)to form corresponding compounds,this comparative experiment is also carried out in the polymer PEG-b-PACMA system.It was found that the exchange reaction between 9-Anthranol terminal group molecule withbenzylamine/benzylalcohol molecule was more efficient and rapid in polymer system.The result of "post-modification" of a polymer system is faster than that of a single molecule system.