Design And Systhesis Of Multifunctional Luminescent Polymer Nanomaterials For Biomedical Applications

Luminescent polymer nanomaterials have attracted extensive attention due to their good optical stability.Particularly,the design and controllable synthesis of multifunctional luminescent polymer nanomaterials with good water solubility and excellent biocompatibility are of great importance for further applications in biomedical field.Firstly,two new Eu（Ⅲ）-containing luminescent polymer nanomaterials were prepared by polymerization-induced self-assembly（PISA）and reflux-precipitation polymerization,respectively.Their applications in tumor cell imaging and cancer therapy were explored.Secondly,a conjugated polymer nanomaterial with near infrared-II（NIR-II）photothermal properties was successfully prepared.The NIR-II light-responsive hydrogel containing the conjugated polymer nanomaterials was constructed as drug delivery system.The potential anti-tumor application in chemo-photothermal synergistic cancer therapy was studied.The main research contents of the dissertation are as follows:1.Water-soluble europium-containing nanoprobes prepared by polymerization-induced self-assembly and their cellular imaging applications.As macro-CTA,the hydrophilic Poly（PEGMA）was controllably synthesized via reversible addition-fragmentation chain transfer polymerization（RAFT）.The luminescent Eu（Ⅲ）-based copolymer nanoparticles Poly（PMEu）NPs was readily prepared by hydrophobic Eu（Ⅲ）-based monomers（Eu（TTA）₂（AA）phen）and methyl methacrylate（MMA）,using Poly（PEGMA）-CTA as hydrophilic macro-CTA via RAFT polymerization-induced self-assembly（PISA）.The resulted Poly（PMEu）nanoprobes showed spherical in good monodispersity with average diameters of around 210 nm.The Poly（PMEu）nanoprobles had excellent aqueous dispersity,high aqueous stability,and good luminescence properties with a quantum yield of 37.2%and a fluorescence lifetime of 312.4μs.Moreover,the Poly（PMEu）nanoprobes exhibited good cellular biocompatibility with cell viabilities of 88.2%and high fluorescence intensity for in vitro cellular imaging.The present approach provided a facile strategy for fabricating luminescent Eu（Ⅲ）-based nanoprobes with significant potential applications for biological imaging.2.Europium（Ⅲ）-containing nanohydrogels for cellular imaging and drug delivery applications.The Eu（Ⅲ）-based nanohydrogels PAAEu NGs were obtained by a facile reflux-precipitation polymerization of monomers（acrylic acid（AA）and Eu（TTA）₂（AA）phen）and the disulfide containing crosslinker bis（2-methacryloyl）oxyethyl disulfide（BMOD）.The resultant PAAEu nanohydrogels（NGs）exhibited excellent monodispersity,high aqueous stability,and vigorous fluorescence intensity with a quantum yield of 22.5%and a fluorescence lifetime of 445.1μs.Due to the presence of negatively charged carboxyl groups,the Eu-containing PAAEu NGs could be employed as drug nanocarriers for positively charged drugs through electrostatic interactions.In this work,the anticancer drug DOX was used as a model drug to evaluate the potential application of PAAEu NGs for drug delivery.The drug loading capacity（DLC）of DOX in PAAEu NGs could reach80.8 wt%.Then the apoptosis/necrosis of He La cells incubated with DOX@PAAEu NGs was explored by flow cytometry.The result was that the release rate of DOX could be significantly enhanced due to the low p H and high GSH concentration.Therefore,PAAEu nanohydrogels could be employed as theranostic nanomaterials for bioimaging and drug delivery applications.The present approach provided a facile strategy for designing Eu（Ⅲ）-based nanomaterials for bioapplications.3.Semiconductor polymer composite hydrogels with NIR-triggered drug delivery for localized chemo-photothermal synergistic therapy.Firstly,a conjugated polymer Poly（TTQ-co-BT-co-2Tc）with near infrared-II（NIR-II）photothermal properties was successfully prepared.Then,the PTBT NPs were prepared via a nanoprecipitation approach using an amphiphilic copolymer Pluronic F127as the stabilizer to encapsulate the poly（TTQ-co-BT-co-2Tc）polymers into the hydrophobic core of the NPs.Secondly,NIR light-responsive PTBT-BTZ@Gel BL were prepared by wrapping PTBT NPs and anticancer drug BTZ in lactose hydrogel Gel BL.This result revealed that the BTZ and BT-NPs were effectively accumulated at the tumor sites,and BT-NPs had an efficient photothermal conversion in vivo.Finally,the semiconductor polymer composite hydrogels achieved excellent chemo-photothermal synergistic therapeutic efficacy.