Radioactive Iodine Nanopolymersomes For Cancer Multimodal Imaging And Therapy

Radionuclides emit photons or charged particles during decay.Photons have strong penetrating power that can be used for diagnosis and study of pharmacokinetics and metabolism of drug in vivo.Charged particles can cause DNA strands breaks and induce cell death,and are widely used in treatment of diseases in the clinics.However,due to their short biological half-life,low accumulation in the pathological site,and radiation damage to normal tissues,radionuclides are not so effective for diagnosis and treatment.Recently,the development of nanocarriers for targeted delivery of radionuclides to the lesion site has become a hot topic.Nanopolymersomes have advantages of good biocompatibility and biodegradability,are able to load drugs and change the biodistribution of drugs in the body,increase drug circulation time,and improve drug efficacy,greatly reducing toxic side effects.Here,combining nanopolymersomes and radionuclides,we prepared radiolabeled nanopolymersomes for diagnosis and internal radionuclides therapy.Further,nuclear imaging was used to evaluate the in vivo circulation,biodistribution and pharmacokinetics of nanopolymersomes:In clinical diagnosis,SPECT can provide high-sensitivity functional imaging,while CT provides structural imaging with high spatial resolution.The combination of SPECT/CT can overcome the the limitations of single modal diagnosis.To this end,we designed radioactive iodine-rich nanopolymersomes for tumor dual modal imaging and internal radionuclide therapy.The pharmacokinetics and biodistribution of radiolabeled nanopolymersomes was studied.In the second chapter,based on the iodine-rich polymer by isotopic exchange reaction,we developed nanopolymersomes(I-PS)with radioiodine(125I and 131I)for SPECT/CT dual modal imaging and interanal radionuclides therapy.The physical morphology of I-PS was characterized by using dynamic light scattering(DLS)and transmission electron microscope(TEM).Cytotoxicity of 125I-PS and 131I-PS was studied by MTT cell proliferation experiment assay.In vitro and in vivo dual imaging of 125I-PS was investigated by microSPECT/CT.Further,therapeutic effect of 131I-PS was tested in 4T1 tumor bearing mice.The results of DLS and TEM showed that the size and morphology of 1251-PS were similar to those of I-PS.MTT assays displayed that I-PS and 125I-PS were non-cytotoxic while 131I-PS caused significant death of 4T1 cells at 5 mg mL-1 with radioactivity 12 ?Ci.Pharmacokinetic and biodistribution studies showed that 125I-PS had a prolonged circulation and distributed mainly in the tumor and reticuloendothelial system.The intravenous injection of 125I-PS to 4T1 murine breast tumor-bearing mice allowed simultaneous high sensitivity and high-spatial resolution imaging of tumor by SPECT and CT,respectively.The therapeutic studies revealed that 131I-PS could effectively retard growth of 4T1 breast tumor and significantly prolong mice survival time.H&E staining assay proved that 131I-PS induced tumor cell death.I-PS emerges as a robust and versatile platform for dual modal imaging and targeted radioisotope therapy.In the third chapter,we modified density of cRGD on the surface of 125I-PS and explored the ability of cRGD-125I-PS to target U87 brain glioblastoma tumor.The physical properties,morphological and stability of cRGD-125I-PS were investigated by DLS and TEM.In vivo targeting ability of cRGD-125I-PS was imaged by microSPECT/CT.The results showed that the cRGD density of cRGD-125I-PS didn't influence the size and morphology of cRGD-125I-PS.Both I-PS and cRGD-125I-Ps showed excellent stability in vitro.Interestingly,the targeting ability of cRGD-125I-PS was found to depend on cRGD density,in which cRGD-125I-PS with a cRGD surface density of 30%exhibited the highest uptake of 7%ID g-1 in U87 tumor bearing mice,as revealed by microSPECT/CT.In conclusion,radioactive nanopolymersomes have been developed based on biocompatible PEG-b-PIC copolymer for cancer multimodal imaging and interanal radionuclides therapy therapy.