Construction Of Drug Delivery System Based On Fenton Effect And Mechanism Of Anti-Tumor Function

Amelioration of solid tumor hypoxia is one of the promising therapeutic strategies for malignant tumor ablation.In particular,reactive oxygen species（ROS）-induced apoptosis has been proved to be an efficient tumor therapeutic approach,relying on advanced drug delivery and rapid generation of ROS in the tumor region.However,tumor hypoxia severely limits the production of ROS within the tumor.The development of nanotechnology and nano-drug carriers provides a favorable platform for tumor treatment.Therefore,how to design and construct an advanced nano-drug delivery system to generate ROS effectively in tumor regions is an effective anti-tumor approach.Herein,a new nanostructure based on biodegradable mesoporous magnetic nanocubes（MMNCs）were prepared as carrier in this thesis,and MMNCs@PCM@Vc were synthesised as nano drug control system specifically targeting tumor cells for ROS self-generation and self-enhancement.This research was focus on the magnetic thermotherapy and ROS combination therapy of tumor.1.In the article,Prussian Blue nanocubes（PBNCs）were first synthesized by hydrothermal method and uesd as the precursors,MMNCs were obtained by calcination at high temperature and used as nano-drug carrier.Then,the MMNCs were loaded with Vc（produce H₂O₂）via a PCM,and modified with bio-targeting molecule folic acid（FA）through an amidation reaction to prepare a nano-drug control system（MMNCs@PCM@Vc）with magnetic and biological targeting function.Hyperthermia triggers Vc release under an operation alternating magnetic field（AMF）and serving as the original source of ROS（endogenous H₂O₂）generation.In addition,MMNCs possess Fenton activity in an acidic environment for ROS-enhancement,which can cause severe damage to tumor cells.2.The morphology and size of different as-synthesized nanoparticles were investigated by transmission electron microscope（TEM）and scanning electron microscope（SEM）.X-ray diffraction（XRD）was used to detect the crystal type of the as-synthesized nanoparticles.Raman technology was used to distinguish iron oxide types.Vibrating Sample Magnetometer（VSM）was used to measure the magnetic properties of the as-synthesized nanoparticles.N₂adsorption-desorption measurements was used to investigated the porosity and specific surface area of the as-synthesized nanoparticles.X-ray photoelectron spectroscopy（XPS）was used to reveal the purity and chemical composition of the as-synthesized nanoparticles during the preparation process.The surface charge of the as-synthesized nanoparticles was detected with a zata-potentiostat.3.The characterization results showed that:MMNCs wereγ-Fe₂O₃structure.MMNCs and MMNCs@PCM@Vc exhibited excellent magnetic properties,regular morphology and uniform particle size distribution.Moreeve,MMNCs@PCM@Vc possess good Fenton-like effect and can produce a large number of hydroxyl radicals（·OH）.MMNCs@PCM@Vc nanoagents showed favourable Magnetic Resonance Imaging（MRI）,Photoacoustic Imaging（PAI）,and near Infrared Thermal Imaging（ITI）multimodal imaging capability in vivo and in vitro.4.The anti-tumor results showed that the in vitro MMNCs@PCM@Vc drug delivery system showed significant magnetic hyperthermia and ROS-enhancement synergistic therapeutic effect.In vivo,MMNCs@PCM@Vc could effectively achieve tumor ablation and inhibits tumor volume increase through the magnetic hyperthermia and ROS combined therapy.Thereby the survival rate of mice was prolonged.5.Finally,a series of biological safety of MMNCs@PCM@Vc were evaluated.Through MTT assay,hemolytic ratio,prothrombin time,activated partial thromboplastin time,thrombin time,standard blood biochemistry and hematology assays,H&E staining,and biodegradability,all the experimental results indicated that the excellent cell compatibility,blood compatibility and histocompatibility of the MMNCs@PCM@Vc nanoplatform.6.In summary,it revealed that this nanoplatform can be combined with magnetic therapy and ROS self-generating and self-enhancing for tumor therapy.A new approach was established to overcome tumor hypoxia,and it will be expected to applied to the clinical detection and treatment of cancer.