Abstract
Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.
Highlights
Much smaller tumors and the procedure can be performed intraoperatively when optimal surgical resection is not possible
The preparation process of the 103Pd@Au nanoseeds starts with the synthesis of hollow Au nanoparticles using the bubble template synthesis method developed in our lab[11,12]
Electrochemically evolved hydrogen nanobubbles serve as templates and reduce Au complex ions into metal Au
Summary
Much smaller tumors and the procedure can be performed intraoperatively when optimal surgical resection is not possible. We report a Cu-mediated surface modification process to efficiently incorporate radioactive isotopes to gold nanoparticles from a solution with trace amounts (~10−8 M) of isotopes. Using this method, 103Pd was incorporated onto hollow gold nanoparticles (~120 nm in diameter). A high therapeutic efficacy was observed without noticeable side effects on the liver, spleen and other organs, which are direct results of such high retention rate inside the tumor. These results show promising potential for such therapeutic agents to become a clinically practical treatment modality for unresectable solid cancers
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