Nanotheranostics Based On Semiconducting Polymer:Design,Systhesis And Applications In Tumor Therapy And Antibacterial

Cancer is one of the major threats to the health of human beings wordwile for centuries.Researchers around the world have been devoted themselves to developing more precise and rapid diagnostic strategies to fight against cancer.Due to the complexity and easy metastasis of the tumor environment,a single method to treat cancer is unrealistic.No matter in clinical or scientific research,the treatment of cancer usually requires to comprehensively use various therapies to achieve the maximum therapeutic effect.At present,the treatment methods for cancer mainly include surgery,chemotherapy,radiotherapy,photodynamic therapy and photothermal therapy.In recent years,semiconductor polymer nanomaterials have shown broad application in the fields of chemistry,optoelectronics,and biomedicine thanks to their structural diversity,excellent biocompatibility and optical properties.However,as the key of treatment,semiconductor polymer nanomaterials still have shortcomings such as poor size control,unstable structure and single treatment function during the preparation process.Therefore,it is of great significance to design a semiconductor conjugated polymer nanodiagnosis and treatment platform with stable structure,controllable size,and a combination of multiple treatment methods.The main research contents of thesis are as follows:1.p H/NIR-responsive semiconducting polymer nanoparticles for highly effective photoacoustic image guided chemo-photothermal synergistic therapyMulti-stimulus responsive drug-loaded nanoplatform based on semiconducting polymer nanoparticles are prepared.Poly(diketopyrrolopyrrole-terthiophene)(PDPP3T)nanoparticles coated with p H/thermo-sensitive amphiphilic block polymer PSNi AA were prepared for simultaneous p H/NIR light controlled drug delivery,chemo-photothermal synergistic therapy,and photoacoustic imaging.The obtained PDPP3T@PSNi AA-DOX NPs showed strong NIR absorbance,good photostability,high drug loading capacity,excellent photothermal efficiency,and high PAI brightness.The drug release could be controllably regulated by p H/NIR light stimulus and DOX which released from PDPP3T@PSNi AA-DOX NPs to cell nuclear could also be highly enhanced by NIR light exposure at acidic condition.The PAI-guided chemo-photothermal therapy was then investigated both in vitro and in vivo,which achieved excellent synergistic therapeutic efficacy and could potentially avoid hyperthermia by PTT and severe side effects by chemotherapy.2.Semi-interpenetrating technique directed fabrication of semiconducting nanoparticles with high drug loading efficiency for chemo/photothermal combined cancer therapyA semi-interpenetrating strategy to prepare highly stable and multi-responsive PDPP3T@PNIPAMAA IPNs is first demonstrated.This approach is simple,easily operated and reproducible.The particle sizes are controllable and their polydispersity index are extremely low.A permanent entangling network with“reinforced-concrete”structures for PDPP3T@PNIPAMAA IPNs has been simultaneously formed,which could avoid particle dissociation and is resistant to organic solvent such as ethanol and THF.Due to the presence of three-dimensional cross-linked structure,PDPP3T@PNIPAMAA IPNs show significantly high drug loading efficiency.A combination of p H/light/GSH-responsiveness,excellent photothermal efficiency and bright PA imaging capacity was obtained for PDPP3T@PNIPAMAA IPNs since PDPP3T and PNIPAMAA entangled together with no chemical bond and both constituents may retain their own properties.In vitro and in vivo results indicate that PDPP3T@PNIPAMAA-DOX IPNs are able to release drugs at controlled rate by p H/light/GSH regulation and offer PAI-guided chemo/photothermal combined therapy with excellent therapeutic efficacy.This approach may be generally extended for the preparation of a wide range of organic polymer nanoparticles to achieve ultrahigh structural stability,precise particle size controllability and excellent drug loading capacity.3.Semi-interpenetrating polymer network based on semiconducting nanoparticles for antibacterial applicationA semi-interpenetrating network structure(PDPP3T@P(NIPAM-DMAEMAQ)IPNs)using the semiconductor conjugated polymer PDPP3T as a photothermal reagent was successfully prepared by the semi-crosslinking interpenetrating technique as the"skeleton"of the quaternary ammonium salt antibacterial group DMAEMAQ.The antibacterial agent PDPP3T@P(NIPAM-DMAEMAQ)IPNs has a particle size of about 120 nm,good dispersibility and excellent photothermal performance and biocompatibility.In addition,the antibacterial effect of photothermal/quaternary ammonium salt of PDPP3T@P(NIPAM-DMAEMAQ)IPNs with S.aureus(Staphylococcus aureus)and E.coli(Escherichia coli)was proved to be beneficial even under conditions of lower concentration(10?g/m L)and laser power density(0.6 W/cm~2).The antibacterial mechanism of PDPP3T@P(NIPAM-DMAEMAQ)IPNs was also explored,which indicating that PDPP3T@P(NIPAM-DMAEMAQ)IPNs kill bacteria by destroying bacterial cell wall and extracellular membrane under NIR laser irradiation.