Application Of Covalent Organic Framework-Based Nanomotor In Anti-Tumor And Thrombus Therapy

As a disease with high mortality,cancer has been the focus of scientists around the world to achieve accurate treatment of cancer.Traditional treatment methods,such as surgical treatment and drug treatment,have the disadvantages of high recurrence rate,serious side effects and multi-drug resistance.Photodynamic therapy and photothermal therapy have received widespread attention in the basic research and clinical application of cancer treatment because of their few adverse reactions and short treatment period.In the active treatment of cancer,the complications of thrombosis are often ignored.Thrombosis related diseases,including acute myocardial infarction,deep vein thrombosis and ischemic stroke,are one of the cardiovascular diseases that seriously threaten human health.Prevention of such complications can reduce the mortality caused by complications while treating cancer,and achieve efficient and accurate treatment.Covalent organic frameworks（COFs）,as a kind of metal-free multifunctional nanomaterials,have good biocompatibility and have been widely used in the biomedical field.Nanomotors can use external energy to realize self-propulsion in the fluid.Because of their independent movement ability,efficient cargo transportation and deep tissue permeability,they have become an emerging platform for anti-tumor and thrombus treatment.Therefore,the main challenge is to design COF-based self-propelled nanomotor to be applied to multi-functional diagnosis and treatment of cancer and thrombosis treatment.Based on this,two kinds of COF-based nanomotors were synthesized for tumor therapy and thrombus therapy.The main contents are as follows:（1）A biomimetic nanomotor based on COF composed of porphyrin modified COF shell layer and polypyrrole（PPy）core layer was prepared（m PPy@COF-Por）.In the use of 808 nm near infrared light irradiation,m PPy@COF-Por can achieve directional movement through the self-heating swimming force generated by PPy,while relying on its excellent photothermal conversion rate in vivo and in vitro to achieve good photothermal treatment effect.Porphyrin-modified COF have good singlet oxygen generation ability at 660 nm and have potential photodynamic therapy ability.The coated HCT116 cancer cell membrane enables the COF-based nanomotor to selectively recognize and reduce adhesion in biological media,resulting in good locomotion ability.Based on the above advantages,the COF-based multi-function nanomotor m PPy@COF-Por has been successfully applied in cancer treatment,and realized photothermal/photodynamic combined phototherapy guided by FLI/IRI/PAI tri-model imaging.（2）Aiming at the thrombus complications caused by unsolved tumor treatment in Chapter 2,a COF with photothermal properties was designed and synthesized,and catalase was loaded on its surface to construct a dual-drive nanomotor（COF@CAT）.It has good photothermal conversion performance under near infrared light,and then converts heat energy into self-driven kinetic energy.Catalase catalyzed decomposition of H₂O₂to produce O₂can provide another power source for COF-based nanomotors.The COF-based nanomotors staying on the surface of thrombus can enter the thrombus under near-infrared light irradiation,overcoming the strong bio adhesion in the biological medium and improving the retention rate of the nanomotors at the thrombus site.In addition,photothermal effect can be specific to thrombolysis,and fluid shear forces in the vein further disperse the clot residue,leading to a reduction in fibrin concentration and the release of blockage.The effect of photothermal thrombolysis was verified by the model of thrombolysis disease.In addition,COF@CAT reduces oxidative stress to vascular endothelial cells by removing excess H₂O₂at the site of thrombus.