One of the limitations of external radiation therapy for metastatic ovarian cancer is delivery of high radiation doses to non-target tissue that can cause significant damage to healthy organs. Image-guided radiotherapy and use of radiosensitizers are effective for localizing, focusing, and delivering external radiation to tumor areas with less damage to the healthy tissues. The current study demonstrates a novel method for synthesizing a family of multifunctional agents composed of two radio-dense elements, gold and tantalum, integrated into a single nanocomposite that can be used for both imaging and radiosensitizing. Dendritic mesoporous silica nanoparticles (dMSNs) with the high surface area were used to integrate these two high atomic number metals in a single nanoplatform. The synthetic approach resulted in stable and monodispersed dMSNs with a uniform distribution of gold nanoparticles on the surface and tantalum oxide in the core. The rationally designed bimetallic nanosystem exhibits strong x-ray attenuation with high-performance X-ray computed tomography (CT) imaging. The CT numbers, measured in Hounsfield units, for the bimetallic nanosystem, is 2.7 times greater than clinically used iodine-based contrast agents at the same concentration making them promising for a combined CT imaging and radiosensitizing application. Preparation, biodistribution, safety, stability and tumor specificity of the designed nanoparticles are reported to establish their feasibility for improving radiation therapy. Cytotoxicity and histological studies confirmed that the designed bimetallic nanoparticles have good biocompatibility with no toxicity observed. Tumor targeting and accumulation of the bimetallic nanoplatform after intraperitoneal administration was demonstrated in a metastatic ovarian cancer mouse model. Micro-CT in conjunction with bioluminescence images showed that the nanoparticles accumulate at the tumor sites. Our work demonstrated that incorporating two radio-dense elements in a single system administrated intraperitoneally provides a new strategy to enhance radiation therapy in metastatic ovarian cancer.

Binary metal-containing nanoparticles for CT imaging and radiosensitization of peritoneal metastatic tumors

2019 Spring National Meeting

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