Synthesis Of Several Conjugated Organic Polymer-based Nanocomposites For Cancer Therapy

The recent research tendency of nanoscience has focused on the development of a new generation of functional porous materials,including conjugated organic polymers with multi-functionality,programmability,adaptability and good biocompatibility.There are kinds of conjugated organic polymers.Among them,covalent organic frameworks(COFs)and covalent organic polymers(COPs)are formed by connecting aromatic organic units through covalent bonds,while hydrogen-bonded organic frameworks(HOFs)are linked by hydrogen bonds.They all have the characteristics of extended conjugated system,high porosity,large surface area and abundant nitrogen-related groups,which have been widely explored in gas storage and separation,heterogeneous catalysis,energy storage,photoelectricity,sensing and drug delivery.Due to these characteristics,conjugated organic polymers can be combined with other materials to form multifunctional materials.These multifunctional materials can be used as drug carriers,photosensitizers and contrast agents for cancer diagnosis and treatment,thus showing great prospects in the field of biomedical applications.Therefore,the design,synthesis and combination of nano-conjugated organic polymer and related composites are of great significance to the development of biomedical nanomaterials.To this end,the main research content can be summarized as follows:(1)Highly monodispersed COF-LZU-1 nanoparticles with an average size of 150 nm were prepared via a mild wet solution method at room temperature.The nitrogen related functional groups of COF-LZU-1 were coordinated with CuSe to form COF-CuSe nanocomposites.Owing to ?-? conjugated structure,the COF-LZU-1 nanoparticles could generate singlet oxygen efficiently under 650 or 808 nm laser irradiation.The photodynamic effect of COF was significantly enhanced after being coordinated with CuSe nanoparticles.The resultant COF-CuSe nanocomposites also exhibited an excellent photothermal effect under 808 nm laser irradiation with a photothermal conversion efficiency of 26.34%.The in vitro and in vivo assessment indicated that the COF-CuSe nanoplatform was an ideal photosensitizer for photodynamic therapy(PDT)and photothermal therapy(PTT)with enhanced antituumor efficacy.Subsequently,COF-Ag2Se nanoparticles were successfully synthesized under mild conditions via a cation exchange approach using COF-CuSe as the template.COF-Ag2Se possessed higher photothermnal conversion efficiency than COF-CuSe,which reached 37.91%.In vitro and in vivo experiments verified the excellent cancer cell killing effect and antitumor efficacy of COF-Ag2Se nanoparticles via combined PDT and PTT.(2)Multifunctional Cu-PPT nanoparticles were synthesized based on the copper acetate catalyzed amino polymerization between p-phenylenediamine and 5,10,15,20-tetra-(4-aminophenyl)-porphyrin at room temperature for the first time.Owing to the Cu2+/Cu+redox couple,Cu-PPT exhibited glutathione(GSH)peroxidase-mimicking capacity to deplete overexpressed GSH in tumor microenvironment(TME)for alleviating antioxidant capability,catalase(CAT)-mimicking ability to relieve hypoxia for improving the production of singlet oxygen and Fenton-like activity to generate·OH to realize chemodynamic therapy(CDT).Moreover,the excellent photothermal effect of Cu-PPT also promoted the CDT process.The synergetic therapy of PTT,PDT and CDT could not only inhibit the growth of primary tumors,but also continuously stimulate systematic antitumor immune responses and reactivate T cells.By further combining with PD-1/PD-L1 mediated CBI,Cu-PPT based therapy could inhibit the growth of distant tumors and suppress tumor metastasis effectively.(3)Fe-MIL-88B-NH2@PFC-1-GOx(abbreviated as MPG)nanoparticles were synthesized by MOF(Fe-MIL-88B-NH2),HOF(PFC-1)and glucose oxidase(GOx)for the first time,realizing synergetic CDT,sonodynamic therapy(SDT)and starvation therapy.MPG nanoparticles exhibited CAT-like,GSH peroxidase-like,and Fenton activities due to the existence of the Fe3+/Fe2+redox couple.Therefore,MPG showed excellent·OH generation ability via the Fenton reaction to realize CDT.MPG could also convert GSH into oxidized glutathione(GSSG)to reduce the antioxidant capacity of cancer cells.In addition,the CAT-like activity enabled MPG to react with H2O2 to generate O2 for relieving hypoxia in TME,further activating the SDT and glucose oxidation process.Thus,PFC-1 nanorods could induce a burst generation of1O2 under ultrasound(US)irradiation to achieve SDT.Meanwhile,the immobilized GOx could catalyze the glucose decomposition in tumor cells to produce gluconic acid and H2O2.As a result,the energy source of tumor cells was cut off to realize starvation therapy.Moreover,the regenerated H2O2 by GOx could enhance the Fenton reaction to realize GOx catalysis-enhanced CDT.In vitro and in vivo experiments demonstrated that MPG based synergetic CDT,SDT and starvation therapy could inhibit tumor growth effectively.