Construction Of Dual Acid And Redox-Responsive Polymeric Fluorescent Probes And Fan-Shaped Amphiphilic Diblock Copolymer-Based Micelles

Amphiphilic diblock polymers containing both hydrophilic and hydrophobic blocks can self-assemble in aqueous solution into various aggregates,such as micelles and vesicles.Since both hydrophilic and hydrophobic small molecules can be spontaneously loaded into the hydrophilic and hydrophobic domains,the selfassemblies formed by amphiphilic diblock copolymers can be used as drug carriers,DNA carriers and imaging agent carriers,and so on.So that the water solubility and physiological toxicity issues of the small drug or imaging agent molecules can be addressed,thus rendering the self-assemblies with potential application value and attracting broad research interest for them.On the other hand,the development of stimuli-responsive polymers that can respond to external stimuli to change their structures,properties and functions,offers better selectivity and sensitivity for the biomedical applications of the self-assemblies based on amphiphilic diblock copolymers.However,more and more functions,such as multi-responsiveness without mutual interfering,are highly demanded in view of the complexity of the microenvironments in cells and living bodies.Therefore,in this context,dual acid-and redox-responsive amphiphilic diblock copolymers were prepared to construct polymeric fluorescent probes,and a series of fan-shaped amphiphilic diblock copolymers were synthesized.This dissertation mainly contains the following two parts.1.Based on the difference between the pH value of physiological environment and cellular endosomes and lysosomes,as well as the different types and concentrations of thiol compounds in cytoplasm and the endolysomes,amphiphilic diblock copolymer,P(MEMA-co-NAM)-b-P(DMA-co-DSF),bearing dichlorofluorescein moieties esterified by ethanthioacetic acid(DSF)and 4-maleimido-1,8-naphthalimide(NAM)moieties in the side chains of the hydrophilic and hydrophobic blocks respectively was synthesized,in which MEMA was methoxy ethyl methacrylate,and DAM was N,Ndimethylacrylamide.Under conditions mimicking the cytoplasmic neutral/weakly alkline pH value,due to Michael addition reaction between the thiol compounds and NAM moieties that blocked the photoinduced electron transfer(PET)effect,the nanoaggregates self-assembled from P(MEMA-co-NAM)-b-P(DMA-co-DSF)can exhibit fluorescence "turn on".However,at acidic pH,no distinct fluorescent emission can be detected as a result of the weak reactivity of the thiol compounds,but the fluorescent emission of DSF moieties located in the hydrophilic shell of the nanoaggregates can "turn on" because of the hydrolysis of the ethyl sulfide bond.Moreover,if further increasing the solution pH value to be cytoplasmic neutral/weakly alkaline,as a result of the fluorescence resonance energy transfer(FRET)effect between the NAM and DSF moieties,the fluorescence emission intensity of DSF can be greatly increased,thus fulfilling stimuli-responsive fluorescence imaging on the different microenvironments in cells.2.Using dendritic polyethylene glycol(Dendron-PEG-OH)as the macromolecular initiator and stannous octoate as the catalyst,a series of fan-shaped amphiphilic diblock copolymers,Dendron-PEG-b-PCL with different hydrophobic polycaprolactone block lengths,were synthesized via the ring-opening polymerization of caprolactone monomer.The Dendron-PEG-b-PCL amphiphilic diblock copolymers can selfassemble in aqueous solution into micelles with the size of 100-200 nm.Due to the excellent biocompatibility and the existence of multiple hydroxyl groups at the end of the PCL "fan handle" and the peripheral of the PEG "fan sector",the nanoaggregates formed by Dendron-PEG-b-PCL can be expected to be used as drug or imaging agent carriers after functionalization.