GOLD-NANOPARTICLE-BASED THERANOSTIC AGENTS FOR RADIOTHERAPY OF MALIGNANT SOLID TUMORS

Abstract

Radiation therapy is one of the three major methods of cancer treatment. The fundamental goal of radiotherapy is to deliver high radiation doses to targets while simultaneously minimizing doses to critical structures and healthy normal tissues. The aim of this study is to develop a general, practical, and facile method to prepare nanoscale theranostic agents for more efficacious radiation therapy with less adverse side effects. First, a novel type of gold nanoparticle, hollow Au nanoparticles (HAuNPs) which was synthesized using the unique bubble template synthesis method developed in our lab, are studied in vitro and in vivo to investigate their effect as radiosensitizing agents to enhance the radiation dose during external radiotherapy. The results showed the promising potential of using HAuNPs as radiosensitization agents for efficacious treatment of breast cancer. Second, a novel radiolabeling method is developed to incorporate medical radioisotopes to gold nanoparticles. We incorporate palladium-103 (¹⁰³Pd), a radioisotope currently in clinical brachytherapy, into a hollow gold nanoparticle. The resulting ¹⁰³Pd@Au nanoparticles in the form of a colloidal suspension can be administered by direct injection into tumors, serving as internal radiation sources (nanoseeds) for radiation therapy. The size of the nanoseed, ~150nm in diameter, is large enough to prevent nanoseeds from diffusing into other areas while still small enough to allow them to homogeneously distribute inside the tumor. The therapeutic efficacy of ¹⁰³Pd@Au nanoseeds have been tested when intratumorally injected into a prostate cancer xenograft model. The findings showed that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors. Finally, to make real clinical application more plausible, multi-functional magnetic nanoseeds nanoparticles for imaging-guided radiotherapy are synthesized and characterized.