Engineering Of Metal-Phenolic Network Microcapsules For Biological Applications

Cancer is one of the diseases that seriously affect human health.In 2020,new cancer cases in China accounts for 23.7%of the total number,which is the highest one,all over the world.At present,although a variety of anti-cancer drugs have been developed,due to the complex biological barrier in vivo,the bioavailability and stability of drugs are not ideal while the side effects are high,which leads to the unsatisfactory treatment effect.In recent years,drug delivery carriers(e.g.,liposomes,inorganic nanoparticles,polymer nanoparticles)with different physicochemical properties have drawn widespread attention,which could effectively improve the bioavailability and reduce the side effects.However,there are still some challenges such as biosafety problems,low drug loading efficiency and complex preparation procedures.Therefore,the development of a safe and efficient delivery carriers with high drug loading capacity is the key for the development of nanomedicines.In this thesis,zeolitic imidazolate frameworks nanoparticles(ZIF-8 NPs)are used as templates to prepare metal-phenolic network(MPN)capsules with pH responsiveness as drug carriers for the exploration of its application in combination cancer therapy.In general,the main contents of this thesis include the following three chapters.Chapter Ⅰ mainly introduces the concept of metal-phenolic chemistry,the category of materials based on metal-phenolic coordination,as well as the construction and tunable properties of MPN capsules.The applications of MPN-based materials in cancer therapy and diagnosis are also summarized.In chapter Ⅱ,ZIF-8 NPs with good dispersibility and controllable size are synthesized based on the biological mineralization of poly(ethylene glycol)(PEG),MPN capsules with controlled sizes,shell thickness and the components of multiple metal ions are fabricated through the prepared ZIF-8 NPs as templates.To demonstrate the potential applications in tumor cell suppression,glucose oxidase(GOx)-encapsulated MPN capsules are prepared using ZIF-8 NPs as templates.The existence of GOx can consume a large amount of glucose at the tumor sites and result in starvation treatment.On the other hand,hydrogen peroxide produced from the glucose decomposition reaction could react with iron ions in MPN capsules to produce toxic hydroxyl radicals,thus playing a vital role in chemodynamic therapy.This work provides a simple and efficient strategy to prepare multi-functional nanomedicine,which are promising for combination cancer therapy.In chapter Ⅲ,MPN-based multifunctional microcapsules are fabricated via coordination and self-assembly method using catalase(CAT)-encapsulated ZIF-8 NPs as templates.The photosensitizer of Chlorin e6(Ce6)can be loaded onto the capsules via the coordination between carboxyl and Fe3+.The results show that Ce6 can induce the production of reactive oxygen species(ROS)under 660 nm laser irradiation.In addition,the encapsulated CAT can promote the conversion of excess H2O2 into O2,which could improve the hypoxic environment of tumor and improve the effect of photodynamic therapy.