Controllable Preparation And Biomedical Application Of Covalent Organic Frameworks

Covalent organic frameworks（COFs）and covalent organic polymers（COPs）are a kind of highly ordered and periodic porous organic polymers synthesized by dynamic reversible chemical bonding.Due to its inherent porosity,wide range of functionality,design flexibility and good biocompatibility,in addition to its conventional applications in energy storage,catalysis,sensing and separation,it has also shown a broad application prospect in biomedical field in recent years.Especially in anti-tumor therapy,including drug delivery,photodynamic therapy（PDT）,photothermal therapy（PTT）,chemodynamic therapy（CDT）and combination therapy.The main content of this paper is to synthesize organic polymer materials with uniform size and controllable morphology at room temperature,and functionalize them to get nanocomposite system,so as to break the limitation of single treatment method.Therefore,this paper mainly carried out the following work:1.COF based on 1,3,5-tris（4-aminophenyl）benzene（TAPB）and 1,3,5-benzenetrialdehyde（BTCA）was synthesized by Schiff base condensation reaction as photosensitizer and carrier.The larger specific surface area improves the load efficiency of ICG and OVA,reaching 29.3 wt%and 40.44 wt%respectively.Under 650 nm and808 nm laser irradiation,COF@ICG@OVA nanoparticles can release heat and produce¹O₂,which can effectively kill CT26 cells,release antigen and activate the body’s immune response.We further combined checkpoint blocking therapy to block the escape of cancer cells.In vivo and in vitro evaluation showed that compared with a single treatment method,COF@ICG@OVA-mediated photodynamic therapy and photothermal therapy combined with checkpoint blocking therapy can inhibit the growth of primary tumor and avoid the metastasis and recurrence of tumor.2.Iron-doped poly（2-nitro-1-phenylene diamine）multifunctional COP was synthesized at room temperature.The synthesized Fe-PNPD-ICG（FPIs）was used for the combined therapy of photothermal（PTT）/photodynamic（PDT）/chemodynamic therapy（CDT）.Once Fe-PNPD-ICG（FPIs）is internalized into the cancer cells,it triggers the Fenton reaction to produce·OH,and clears the over-expressed glutathione（GSH）in TME,thereby reducing the antioxidant capacity in the tumor.At the same time,the generated oxygen can reduce hypoxia in TME and enhance the therapeutic effect of PDT.More importantly,FPIs shows excellent photothermal effect with a photothermal conversion efficiency ofη=36.65%.3.Fe²⁺doped covalent organic frameworks（COF）was synthesised and applied as template to grow Ca CO₃shell.Then O₂ was storaged into Fe²⁺doped COF,forming O₂-Fe COF@Ca CO₃nanocomposite.Besides,COFs can induce the production of ¹O₂ under650 nm irradiation for photodynamic therapy（PDT）.Low p H and hypoxia in tumour microenvironment（TME）can activate the nanocomposite to release oxygen and Ca²⁺.The released O₂ can alleviate hypoxia in TME,thus enhancing the efficiency of COF-mediated PDT.Abundant Ca²⁺were released and accumulated in cancer cells,resulting in cancer cell apoptosis.After modification with folic acid（FA）,O₂-Fe COF@Ca CO₃@FA（OFCCF）can target breast cancer cells and realize PDT/Ca²⁺overload synergistic treatment.