Macrophages Loaded With Germanium And Zirconium Nitride Nanoparticles For Photo Therapy Of Tumors

As an emerging cancer treatment method,phototherapy has lower invasiveness and less side effects than traditional surgical treatment,chemotherapy and radiotherapy,and it has broad clinical application prospects.The development of targeted bioactive nanomaterials with high biocompatibility and the realization of phototherapy for rabbits with orthotopic tumor have important clinical significance for the treatment of human deep tumor.Macrophages can carry large numbers of particles and target tumor sites.In this thesis,two photoactive materials Ge/GeO₂ and Zr N nanoparticles were selected and loaded by macrophages for targeted phototherapy of tumors.The ultraviolet-visible-near infrared absorption spectrum showed that the Ge/GeO₂ nanoparticles synthesized in this thesis had a wide range of light absorption in the near infrared region.The chemical composition and valence state were characterized by transmission electron microscope and X-ray diffraction energy spectrum.In vitro cell experiments showed that Ge/GeO₂ nanoparticles could simultaneously produce active oxygen and heat under the irradiation of near infrared light.After loaded in macrophages,Ge/GeO₂ can be targeted to reach the tumor by intravenous administration,and completely clear solid tumors in mice.This thesis also used B-ultrasound to observe the evolution of the tumor after phototherapy,and found the sequential process of tumor necrosis,liquefaction,softening and eventual disappearance.In addition,the cytotoxicity and hematological toxicity of Ge/GeO₂ studied in this thesis were negligible,especially after being loaded by macrophages.The Zr N nanoparticles selected in this thesis had broad and strong light absorption.Cell experiments showed that Zr N nanoparticles could produce singlet oxygen and have a photothermal effect under near infrared light irradiation,which was an ideal candidate material for tumor ablation.At the same time,when macrophages were used as cell carriers to carry Zr N nanoparticles,the photophysical properties were not affected.Tumor phototherapy was performed by intravenous injection in mice.B-ultrasound showed that the tumor was completely ablated.By monitoring the temperature of the tumor site in mice,it can be proved that Zr N nanoparticles were transported to the tumor site.In order to study the phototherapy effect of Zr N nanoparticles carried by macrophages in large animal with orthotopic tumors,the next step was to treat rabbit breast cancer by intravenous injection into the ear margin.The contrast enhanced ultrasound results showed that the rabbit solid tumors were completely cleared.Macrophage-loaded Zr N nanoparticles can effectively mediate synergistic phototherapy,and the treatment did no harm to mice or rabbitsIn summary,the Ge/GeO₂ nanoparticles and Zr N nanoparticles in this thesis have high absorption in the near infrared region,and they are two types of phototherapy materials that have both photothermal properties and photosensitive properties.At the same time,macrophages are good targeting carriers,which can not only engulf large doses of nanoparticles,but also target Ge/GeO₂ nanoparticles and Zr N nanoparticles to the tumor site without changing the performance,and it can successfully ablate tumors in mice and rabbits.