Construction Of NIR Fluorescent Nanoprobes And Dendrimers Based On Self-Immolative Polymers

Self-immolative polymers(SIPs)can be rapidly degraded upon the cleavage of the triggering motifs at the chain end under external stimuli(including pH,temperature,redox conditions,ions,enzymes,and light,etc.).The difference between traditional stimulus-responsive degradable polymers and SIPs is that SIPs can be converted into many small molecular fragments through a series of tandem depolymerization reactions similar to the domino effect after the triggering moiety is removed,thus exhibiting amplified responsiveness to external stimuli.In addition,the aggregation-induced fluorescence quenching properties of most fluorescent molecules can be integrated with stimuli-responsive polymers to more effectively exert the performance of fluorescent molecules under certain specific circumstances.Based on above,in this thesis we synthesized an acid-responsive self-degradable polymer to construct a near infrared(NIR)fluorescent nanoprobe,and its self-degradation process,the fluorescence activation ability in acidic environment,photothermal and photodynamic properties,as well as its biological specific imaging function were explored.Besides,an amphiphilic dendritic polymer with a precise structure was prepared based on self-degradable polymers,and its self-assembly performance was explored.1.Polyurethane with maleimide moieties suspended in the side groups is obtained by the efficient reaction between isocyanate group and hydroxyl group.After being terminated with Schiff base structure,the hydroxyl group at the other end of the polymer chain was coupled with monomethoxy polyethylene glycol mPEG-CON3 via the reaction with acyl azide terminal through a one-step method to obtain an amphiphilic acid-responsive diblock SIPs.Finally,the near-infrared fluorescent dye IR820 motif was introduced into the side groups of the carbamate segment through the Michael addition reaction of sulfhydryl-maleimide to prepare the degradable TnbsP(IR8200.67-co-MI0.33)6-b-PEG2k.The non-degradable amphiphilic diblock copolymer,Tba-P(IR8200.5-co-MI0.5)6-b-PEG2k,terminated with a benzyl alcohol ester structure at the carbamate block end was synthesized following the same process.Both of the obtained polymers can self-assemble in aqueous solution into spherical nanoparticles,in which the IR820 fluorescent moieties were located in the hydrophobic micellar cores composed of carbamate blocks.Due to the aggregation-induced fluorescence quenching effect,the assemblies hardly shows fluorescence emission without triggering event.When the degradable Tnbs-P(IR8200.67-co-MI0.33)6-b-PEG2k nanoparticles were exposed to an acidic environment to trigger the dissociation of the Schiff base structure at the chain end,the carbamate backbone underwent depolymerization leading to the dissociation of the micelle structure.As a result,the fluorescence emission property of the IR820 moieties were activated,and the methylene quinone produced by the degradation could also capture proteins containing sulfhydryl or amino groups in the surrounding environment.At the same time,the fluorescent nano-probe has photothermal and photodynamic properties.The cytotoxicity test results showed that the acidic micro-environment in the cancer cells can effectively activate the fluorescent emission of the fluorescent nano-probe,which meanwhile exhibited prominent ability to kill cancer cells.The results of animal imaging experiments showed that the nanoprobe has excellent tumor imaging specificity and long-term tracing ability.2.A kind of branching monomer unit with a carboxyl group at one end and two aldehyde groups at the other end was designed and synthesized.In the presence of diphenyl azide phosphate(DPPA)and o-nitrobenzyl alcohol with two hydrophobic alkyl chains,the first-generation dendrimers with carbamate linkages was synthesized through one-step high efficiency reaction,then the aldehyde groups were reduced to two hydroxyl groups followed by reacting with the branching monomer units to prepare the second-generation dendrimers.Finally,the end hydroxyl groups of the dendrimers were reacted with phenylacyl azide with two methoxytriethylene glycol chains to obtain amphiphilic dendritic polymers with precise molecular weight.The self-assembly behaviors of these polymers were explored and it was found that the assembly morphology gradually changed as the branching generation increased.