Synthesis Of Several Covalent Organic Framework Nanocomposite For Antitumor Application

As a new class of porous crystalline organic materials,covalent organic frameworks(COFs)have played a great role in many research fields due to their predesigned and tunable structures.In recent years,COFs have also shown great potential in biomedical,especially anti-tumor applications.They have been applied in drug delivery and phototherapy,showing considerable therapeutic effect.However,the traditional synthesis method of COFs with harsh reaction conditions cannot play an effective role in the regulation of the product including morphology and size,which makes COFs unable be widely used for biomedical applications.In addition,monotherapy has certain limitations,and its therapeutic effect is usually unsatisfactory when dealing with complex tumor microenvironments,especially malignant tumors.Therefore,the development of mild and facile synthetic methods to prepare multifunctional COFs-based nanocomposite systems with suitable size and good biocompatibility for multimodal cancer therapy will promote the further development of COFs in biomedical applications.In this paper,we mainly carried out the following work aiming at the problems mentioned above:(1)Firstly,TAPB-DMTP-COF was synthesized by stirring at room temperature,and then the anticancer drug doxorubicin hydrochloride(DOX)was successfully loaded into TAPB-DMTP-COF in situ by one-pot method.The obtained DOX@COF composite showed a high drug loading efficiency of 32.1 wt%and pH response release characteristics.The good biocompatibility and enhanc ed anti-tumor efficacy of this nanocomposite was futher proved based on cells and animal experiments.(2)A multifunctional nanocomposite based on COF was designed for synergetic photo-,chemodynamic-,and immunotherapies.Firstly,an imine linked COF with the ability to generate singlet oxygen under 650 nm laser irradiation was synthesized at room temperature.Then the synthesized COF was metallized with FeCl3,and p-phenylenediamine was further polymerized on the surface of COF using Fe3+ as oxidant.The obtained poly(p-phenylenediamine)could be used as an agent for photothermal therapy.Moreover,H2O2 overexpressed in tumors would undergo Fenton reaction with Fe3+/Fe2+ redox pair and be catalyzed to decompose into hydroxyl radical(·OH).At the same time,the high temperature caused by photothermal therapy could accelerate the production of ·OH.Subsequently,tumor-associated antigen combined with immune checkpoint blockade induced a powerful anti-tumor immune response and effectively inhibits tumor metastasis.This COF-based multifunctional nanoplatform provided an effective therapeutic strategy for inhibiting both primary tumors and tumor metastases.(3)A porphyrin-based COF(CTP)nanocubic with good water solubility was prepared via a facile and mild method.Different from the traditional synthesis method of porphyrin-based COFs,this novel strategy greatly shortened the reaction time and decreased the reaction temperature.The synthesized CTP overcame the disadvantages of poor solubility and biocompatibility of monomer,and π-πconjugation was also enhanced,thereby narrowing the band gap.The improved biocompatibility and narrowed band gap enabled CTP an excellent sonosensitizer with enhanced sonodynamic effects.In addition,due to the extended conjugated structure,CTP could also efficiently realize photothermal conversion under external irradiation.Moreover,we also doped porphyrin molecules into COF through monomer substitution strategy to improve the biocompatibility and stability of organic sonosensitizer,so as to improve the sonodynamic therapy effect.This study not only provided an alternative method for the synthesis of porphyrin-based COFs,but also presented a novel strategy to improve the efficiency of sonosensitizers.