Construction Of In-situ Oxygen Generation Multiple Response Nano-system And Research Of Multi-modal Imaging Diagnosis And Treatment

This research has produced a smart responsive nanoparticle that is suitable for targeted drug delivery and smart responsive release for cancer treatment.In this nano-delivery system,the outermost red blood cell membrane（RBC）integrates various functional components,including the targeting function modified by folic acid（FA）ligand and the long circulation function modified by polyethylene glycol（PEG）;the chemotherapy function of the drug doxorubicin（DOX）;polydopamine（PDA）near-infrared laser trigger function;manganese dioxide（MnO₂）microenvironmental response adjustment function and magnetic resonance imaging diagnosis and treatment function.We prepared nano-sized MnO₂particles through the liquid phase co-precipitation method,and coated the outer shell of PDA through the oxidative self-polymerization of dopamine,loaded the chemotherapy drug DOX throughπ-πconjugate and electrostatic attraction,and integrated folic acid and polyethylene in the outer layer.Alcohol-functionalized erythrocyte membrane nanovesicles（RBC/FA）to obtain MnO₂-PDA-DOX@RBC/FA/PEG nanoparticles,which have a variety of response properties,and pass particle size,potential,electron microscopy and infrared.The nano-delivery system was characterized by X-ray diffraction,X-ray photoelectron spectroscopy and other methods.The results showed that the target nanoparticle was successfully prepared,and its particle size was relatively narrow,uniform in size,and spherical in shape;afterwards,it was stabilized.Performance investigation and performance evaluation,the results show that the properties are stable,and have ideal physical and chemical properties and excellent functional characteristics.Under in vitro conditions,the nanoparticles have strong and stable photothermal conversion performance and can respond to near-infrared light（NIR）;The in vitro catalytic ability evaluated the response of nanoparticles to hydrogen peroxide（H₂O₂）in an acidic environment.The results showed that MnO₂-PDA-DOX@RBC/FA/PEG can react with H₂O₂,consume H⁺and produce O₂,so it is suggested that Regulate the potential of hypoxia and acidity of the tumor microenvironment,and at the same time generate the contrast agent Mn²⁺with magnetic resonance imaging function,and this part has been verified in the in vitro MRI experiment.Subsequently,the in vitro release of the drug was investigated,and the release kinetics under different conditions were investigated.The results showed that compared with the bulk drug DOX,the MnO₂-PDA-DOX@RBC/FA/PEG nanoparticles after preparation have a significant slow-release effect,and Under acidic（p H）/near-infrared light（NIR）/redox conditions,the drug release rate is accelerated and the drug release is more complete.After that,in vitro targeted drug delivery and photothermal chemotherapy were further carried out,which proved that the red blood cell targeted combination therapy has a significant synergistic therapeutic effect,which can be effectively taken into tumor cells through active targeting,and successfully achieves dissolution.The enzyme body escapes,smoothly targets the mitochondria,consumes hydrogen ions,generates oxygen,regulates the microenvironment inside the tumor,and produces a large amount of reactive oxygen species,which induces cell apoptosis.Animal experimentshavefurtherconfirmedthat MnO₂-PDA-DOX@RBC/FA/PEGnanoparticleshavegood biocompatibility and higher targeting of active and passive tumor sites,which can significantly reduce the toxic and side effects of DOX on the heart and other organs.It also prolongs the action time of the drug in the body,and can achieve the effect of sustained release.The combination of photothermal therapy（PTT）/photodynamic therapy（PDT）/chemotherapy significantly improves the tumor suppressing effect,and the systemic toxicity and adverse reactions are minimized.In vivo,NIR photothermal,fluorescence and magnetic resonance（MR）multi-mode imaging have shown that nanoparticles have effective tumor specificity through enhanced permeability and retention（EPR）effects and active targeting of folate ligands Sex enrichment can effectively deliver loaded drugs to tumor tissues and significantly improve tumor hypoxia,which further promotes the therapeutic effect of PDT/PTT in vivo.In short,we have developed a smart in-situ oxygenation-responsive multifunctional nanoparticle,a coordinated chemotherapy and photothermal treatment method,with a p H-/NIR-/redox-multiple response,its high spatial and temporal controllability,It can release drugs on demand,and can produce oxygen in situ,which can effectively improve the tumor microenvironment.It can also be used as an imaging and diagnostic agent in the clinic.This article provides a novel strategy.It has a good reference value in diagnosis and treatment.