Radiation Therapy Of Tumor Based On Metal-organic Framework PCN-224 Nanomaterials

Radionuclides of ionizing radiation have been used to diagnose and treat various diseases,especially cancer.The charged particles emitted by radionuclides can induce DNA double-strand breaks and apoptosis of cancer cells.However,the short circulation time of free radionuclides,nonspecific distribution and physiological toxicity hinder the wide application of radioisotope therapy.Therefore,in order to solve the problem faced by radiation drugs,people began to explore various functional nanomaterials for radiolabeling to achieve comprehensive tumor imaging and improve the efficiency of RIT treatment.Nanoscale metal-organic frameworks(nMOFs)have been widely used in biomedical applications including cancer imaging and drug delivery.However,there have been rare reports utilizing nMOFs as a single nanoplatform to label various radionuclides for tumor imaging and radioisotope therapyAccordingly,we developed a polyethylene glycol(PEG)modified zirconium-based nMOFs(PCN-224)with good size,water solubility and biocompatibility.The successful synthesis and noteworthy properties of PCN-PEG nanomaterials were verified by various characterization methods.Interestingly,in the absence of chelating agents,metal radionuclides(technetium-99m/99mTc,lutetium-177/177Lu)can be effectively labeled on PCN-224 by chelating the porphyrin structure,while iodine-125(125I)can be labeled on PCN-224 by chemically substituting the hydrogen on the benzene ring.Moreover,the radionuclide-labeled PCNPEG nanoparticles showed good radiolabeling stability in different solutions.Then we studied the tumor treatment application of the nanomaterials at the cell and living level respectively.We found that pure nuclide and unlabeled PCN-PEG have no acute toxicity,while the 177LuPCN-PEG taken up by tumor cells can destroy the cells.Inner macromolecules,and then induce cell apoptosis.According to the fluorescence imaging of PCN-PEG-injected mice,SPECT/CT imaging showed that 99mTc-PCN-PEG has longer blood circulation time and higher tumor aggregation ability.In addition,177Lu-PCN-PEG can significantly inhibit the growth of tumors,and has no obvious toxicity to mice.In addition,we successfully loaded ultra-small gold nanoparticles on the surface of PCN-224 by reduction method and wrapped them with manganese dioxide,and successfully prepared PCN-Au@MnO2 nanoparticles with good size,morphology and dispersibility,and they are expected to be used to improve tumors.The hypoxic environment in treatment enhances the coordinated treatment direction of radiotherapy and photodynamic therapy.To sum up,we use two methods to prepare nanoparticles based on the nano-metal organic framework PCN-224.PCN-PEG nanomaterials,as a new type of fluorescent imaging and radionuclide-labeled nanomaterials,have incredible potential in the field of tumor theranostics.In addition,the PCN-PEG nanoparticle-based platform can also combine Cerenkov radiation and photodynamic therapy and its photosensitivity properties to explore tumor treatment,and further overcome the penetration problem of photodynamic excitation light in future work.PCN-Au@MnO2 nanoparticles will also have great potential in the field of tumor treatment.Therefore,the nano-delivery platform based on PCN-224 will provide more opportunities for the precise treatment of tumors and the expansion of the biomedical applications of MOF nanomaterials.