Design Of Stimuli-responsive Type Biomimetic Nanozyme Carrier And Its Antitumor Research

In recent decades,the design and application of nanocarriers have made great progress in the field of cancer treatment.Through the ingenious design of the carrier,it can effectively reduce the low availability,toxic side effects of the drug and bioactive molecule in the tumor treatment process.The introduction of various new therapies such as photodynamic therapy and chemical kinetic therapy has also provided more ideas for the design of carriers.In particular,some stimuli-responsive carriers can achieve the purpose of fixed-point release of tumor sites according to the characteristics of hypoxia and slightly acid in the tumor site.This study designed two kinds of carriers based on Chemodynamic Therapy?CDT?,through erythrocyte membrane camouflage,fixed-point release of tumor sites,etc.,to improve the efficiency of enzyme and drug delivery,and reduce system toxicity.The concentration of H₂O₂ in the tumor site is increased by glucose oxidase and superoxide dismutase to enhance the effect of chemical kinetic therapy.The main research work is as follows:?1?Chain-stimulating response type bionic nanozyme carrier for tumor therapy.Biomimetic approach and combination therapy offer a novel and efficient route to design Bionic carrier with enhanced antitumor performance and biocompatibility.In this work,red blood cell?RBC?membrane camouflaged glucose oxidase?GOD?and"biomimetic peroxidase-iron nanoparticles"?G-M@RBC?are fabricated for synergistic Cancer Starvation Therapy?CST?and CDT.Angiopep-2 peptides was incorporated onto the surface of RBC membrane carrier?G-M@RBC-A?to improve C6 tumor targeting efficiency.When photosensitive reagent was stimulation by an 808nm near-infrared?NIR?laser,the RBC membrane would be disrupted by the light-induced photothermal heating and singlet oxygens,resulting in enzymes release.Enzymes can penetrate into the interior of the tumor by virtue of its minor particle size.Subsequently,"glucose oxidase"oxidizes the abundant"glucose"in the tumor into"gluconic acid"and"hydrogen peroxide",consuming glucose for CST while providing a large amount of hydrogen peroxide for the next reaction,followed by"iron"catalyzes the"hydrogen peroxide"to produce a strong hydroxylation reaction?Fenton reaction?of"hydroxyl radical?·OH?"for killing tumor cells.Subsequent cell and in vivo experiments demonstrate that the carrier has good tumor targeting and enzyme-controlled release ability,and combination therapy has a good tumor treatment efficacy.?2?Preparation and Characterization of Biomimetic Metal-Organic Coordination Polymer?MOF?Nanoparticles Loaded Functionalized SOD Enzyme and?-LappaAs a human body-derived substance,enzyme is often used in the treatment of human diseases.Due to the efficient catalytic activity of enzymes,it is easy to react with blood or normal tissues during circulation in the body,and its delivery efficiency is also inefficient.Here,we prepare the biomimetic metal-organic coordination polymer nanoparticle to transport the functionalized SOD and?-lapachone.It can improve the delivery efficiency,and protect SOD and?-lapachone from contact with blood.We successfully obtained a functionalized SOD enzyme?Fe-SOD?with both SOD enzyme activity and peroxidase function by mineralizing iron nanoparticles into the SOD enzyme lumen.Fe-SOD and?-lapach were co-packaged during the formation of ZIF-8 and then camouflaged using a targeted erythrocyte membrane.The detection of SOD enzyme activity and drug release experiments at different pH confirmed that the carrier could degrade in an acidic enviro nment,and the proton buffer effect was used to release the internal enzymes and drugs.