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.

We report in vitro studies on radiotherapy enhancement of hollow gold nanoparticles (HAuNPs), which feature a 50 nm hollow core and a 30 nm thick polycrystalline shell. A clonogenic cell survival assay was used to assess radiation dose enhancement on breast cancer MDA-MB-231 cells. Cells were cultured in a cell culture solution in which pegylated HAuNPs were added. No cytotoxicity of the HAuNPs was observed at the nanoparticle concentration up to 4.25×109 nanoparticles/ml (350 μM Au concentration). A small animal X-ray irradiator and a clinical linear accelerator were used to irradiate HAuNP-treated and control groups. It shows that the radiation damage to the cells is significantly enhanced when the cells are exposed to HAuNPs. This is the first time that AuNPs with diameter larger than 100 nm has been studied for their radiosensitizing effects. In clinical settings, we envision that HAuNPs could be intratumorally injected into tumors, which is more realistic for practical usage of AuNPs as radiosensitizer than passive accumulation in tumors using the enhanced permeability and retention effect or active targeting. Larger particles are favored for the intratumoral injection approach since larger particles tend to be retained in the injection sites, less likely diffusing into surrounding normal tissues. So, this proof-of-concept evaluation shows a promising potential to use HAuNPs as radiation therapy sensitizer for cancers.

Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas.

Purpose: Gold nanoparticles have been studied as radiation sensitizers to enhance radiotherapy. It has been reported that hollow shell‐shaped nanoparticles may lead to higher radiation enhancement than solid nanoparticles. We have developed a new gold nanoparticle in the shape of a hollow capsule. In this work we investigate the radiotherapy enhancement of this NanoCapsule system. Methods: Hollow shells nanoconstructs with a diameter of approximately 120 nm were synthesized and used for all experiments. Radiotherapy enhancement was evaluated through cytotoxicity of gold NanoCapsules in MDA‐MB‐231 human breast cancer cells in‐vitro. 100–4000 cells were plated in P60 Petri‐dishes and incubated for 24 hours. Sterilized gold nanoparticles were subsequently added to the cultures, in concentrations ranging from 0–350 μM. 48 hours after plating, cell colonies were irradiated using x‐rays from a small animal irradiator (Precision X‐ray, North Branford, CT) or a 6 MV x‐rays in flattening‐filter free mode from a commercial linear accelerator (Truebeam, Varian Medical Systems, Palo Alto, CA). The cell colonies were fixed 8 days after irradiation, stained, and counted. Results: The total intracellular Au concentration was confirmed by ICP‐Mass spectrometry. Control experiments demonstrated no significant cytotoxicity of Au‐NanoCapsules up to an Au concentration of 350 μM. The radiation enhancement was quantified by analyzing the survival fraction, the ratio between the between the numbers of survival colonies of irradiated samples and control samples (no irradiation). The survival fraction dropped from 0.37 to 0.24 using a Truebeam and from 0.17 to 0.03 with a small animal irradiator at a dose of 4 Gy with an Au concentration of 140 μM. Conclusion: Taking advantage of this novel Au‐NanoCapsule geometric configuration allows for gold nanoparticles to permeate the cell membrane and deliver dose locally, greatly reducing the amount of radiation required to achieve the same local control, whereby minimizing dose to sensitive structures.