Fe@Fe 3 O 4 Nanoparticles In Photoacoustic Imaging-guided Magnetocaloric Therapy And In Vivo Bioorthogonal Reactions

Magnetic hyperthermia has become a very important minimally invasive treatment for tumors by using magnetic hyperthermia effects to generate high temperatures to kill diseased tissues or cells.A magnetic material placed in a high-frequency alternating magnetic field will generate a large amount of heat and can rapidly increase the temperature in the vicinity of the material,which can lead to the death of diseased cells near the material.Magnetic hyperthermia therapy has the characteristics of non-invasive and non-invasive,and there is no limited of tissue penetration,which is one of most ideal method in many therapeutic technologies.Therefore,the development of a magnetic material with good biocompatibility is more meaningful for the research and treatment of tumors.Photoacoustic imaging（PAI）is a non-destructive medical imaging method that has emerged in recent years.It is an imaging mode that inverts the tissue structure based on the absorption distribution of light by biological tissues.When a beam of light hits a biological tissue,the biological tissue absorbs light energy and generates a slight amount of thermal expansion,which generates ultrasonic waves with thermal expansion.The amount of absorbed light energy determines the intensity of the generated ultrasound,so different tissues will produce different intensity ultrasound.According to the detected signal source and intensity to reconstruct the distribution of light energy absorption within the tissue,it can distinguish between normal tissue and diseased tissue.PAI is One of the indispensable tools for biomedical basic research and disease-related applied research.In this work,the first part of the dissertation focuses on the concepts of diagnosis and treatment integration and imaging guided therapy.The Fe@Fe₃O₄ nanoparticles can be prepared by high-temperature pyrolysis method with good particle size uniformity and core-shell structure.In order to solubilize the oleic acid-coated MNPs in the aqueous media,the hydrophobic MNPs was encapsulated with PEG-phospholipids via the van der Waals interaction to form PEGylated MNPs.Considering accurately treat human gliomas that plague human health,the active targeting polypeptide RGD was bound to the nanoprobe surface.By investigating the characteristics of the nanoprobe solution,which was found that it has ideal photoacoustic signals and magnetic hyperthermia properties.In theα_vβ₃-positive U87MG glioblastoma xenograft model,the PA signal of RGD-PEG-MNPs reaches its maximum in the tumor at 6 h after intravenous administration.This signal was enhanced by 2.2-folds compared to that of the preinjection.which provided important information for the next step of magnetic hyperthermia therapy.Under the guidance of photoacoustic experiment results,efficient and active targeted magnetic hyperthermia therapy for human brain gliomas was achieved.The second part of this dissertation is based on Fe@Fe₃O₄ nanoparticle.A DBCO-modified nanoprobe was developed by similar methods.DBCO-modified nanoparticles were used to target the tumor site by using the EPR effect of the tumor.Then,photoacoustic methods were used to study the effect of the Click reaction to target the enrichment of tumor sites of cyanine dyes and explore its in vivo metabolism and biodistribution.Compared with other control groups,the photoacoustic signal value of the pre-targeted experimental group（10 h）increased with time at the tumor site,which quickly reached a maximum at 4 h（4.0 times compared to pre-injection）.With the continuous metabolism of nanoparticles,the photoacoustic signal gradually decreased and the photoacoustic signal value of the tumor site was still 2.4 times that of pre-injection at 48 h,which will have potential for clinical application in the future.