Gold Nanoparticles in Cancer Therapy: Efficacy, Biodistribution, and Toxicity.

Gold-based nanoparticles are utilized for cancer therapeutics as a system for drug delivery, or as a mediator for thermal therapy, whether ablation or hyperthermia. This review discusses how the design of the physicochemical properties of the different types of gold-based nanoparticles affects their treatment efficacy. The basic principles and mechanism at which it mediates heating and delivers drugs efficiently in vivo is also summarized. We will also review the in vivo preclinical data on the biodistribution, intratumoral distribution, cell internalization, and its associated toxicity. Lastly, an updated list of the clinical trials based on nanoparticles and future perspectives are provided.

Photoacoustic- and Magnetic Resonance-Guided Photothermal Therapy and Tumor Vasculature Visualization Using Theranostic Magnetic Gold Nanoshells.

Nanoparticle based image-guided therapy is an emerging technology for cancer in recent years. Here, we report simultaneous photoacoustic (PA)- and magnetic resonance (MR)-guided photothermal ablation (PTA) therapy using multifunctional superparamagnetic iron oxide-containing gold nanoshells (SPIO@AuNS). Based on the intrinsic high near-infrared optical absorbance and strong magnetic property of SPIO@AuNS, we carried out in vivo dual-modality PA-MR imaging of mouse tumors. PA- and MR-guided imaging can monitor therapeutic effect after photothermal therapy mediated by our multifunctional nanomaterial. In addition, using our pulsed laser PA technique, we also observe a clearer structure of the tumor vasculature after intravenously administration SPIO@AuNS. The novel dual PA-MRI image-guided PTA therapy provides a promising new platform for cancer diagnosis and treatment simultaneously.

Percutaneous intraportal application of adipose tissue-derived mesenchymal stem cells using a balloon occlusion catheter in a porcine model of liver fibrosis.

PURPOSE: To investigate the safety and effectiveness of a novel endovascular approach for therapeutic cell delivery using a balloon occlusion catheter in a large animal model of liver fibrosis. MATERIALS AND METHODS: Transcatheter arterial embolization with ethiodized oil (Ethiodol) and ethanol was used to induce liver damage in 11 pigs. Mesenchymal stem cells (MSCs) were harvested from adipose tissue and engineered to express green fluorescent protein (GFP). A balloon occlusion catheter was positioned in the bilateral first-order portal vein branches 2 weeks after embolization to allow intraportal application of MSCs in six experimental animals. MSCs were allowed to dwell for 10 minutes using prolonged balloon inflation. Five control animals received a sham injection of normal saline in a similar fashion. Hepatic venous pressure gradient (HVPG) was measured immediately before necropsy. Specimens from all accessible lobes were obtained with ultrasound-guided percutaneous 18-gauge biopsy 2 hours after cell application. All animals were euthanized within 4 weeks. Fluorescent microscopy was used to assess the presence and distribution of cells. RESULTS: Liver injury and fibrosis were successfully induced in all animals. MSCs (6-10 × 10(7)) were successfully delivered into the portal vein in the six experimental animals. Cell application was not associated with vascular complications. HVPG showed no instances of portal hypertension. GFP-expressing MSCs were visualized in biopsy specimens and were distributed primarily within the sinusoidal spaces; however, 4 weeks after implantation, MSCs could not be identified in histologic specimens. CONCLUSIONS: A percutaneous endovascular approach for cell delivery using a balloon occlusion catheter proved safe for intraportal MSC application in a large animal model of liver fibrosis.

Development of a large animal model of cirrhosis and portal hypertension using hepatic transarterial embolization: a study in swine.

PURPOSE: To develop a clinically relevant porcine model of liver cirrhosis with portal hypertension by means of hepatic transarterial embolization. MATERIALS AND METHODS: Institutional animal care and use committee approval was obtained for all experiments. Pigs received transcatheter arterial infusion of a 3:1 mixture of iodized oil and ethanol into the hepatic artery in volumes of 16 mL in group 1 (n = 4), 28 mL in group 2 (n = 4), and 40 mL in group 3 (n = 4) with intent of bilobar distribution. Hepatic venous pressure gradient (HVPG) measurement, liver function tests, and volumetry were performed at baseline, at 2 weeks, and before necropsy. RESULTS: Cirrhosis was successfully induced in three animals that received 16 mL of the embolic mixture and in all four animals that received 28 mL. The animals in the 40-mL group did not recover from the procedure and were euthanized within 48 h. Increases in HVPG after 6-8 weeks versus baseline reached statistical significance (P < .05). Correlation between degree of fibrosis and volume of embolic agent did not reach statistical significance, but there was a trend toward increased fibrosis in the 28-mL group compared with the 16-mL group. CONCLUSIONS: Transcatheter hepatic arterial embolization can be used to create a reliable and reproducible porcine model of liver cirrhosis and portal hypertension.

Percutaneous transesophageal gastrostomy tube placement: an alternative to percutaneous endoscopic gastrostomy in patients with intra-abdominal metastasis.

BACKGROUND: PEG/jejunostomy (PEG/J) is often placed in patients with metastatic gastric cancer for palliating bowel obstruction or for feeding. However, PEG/J placement may not always be possible for many reasons. OBJECTIVE: We wish to bring attention to the percutaneous transesophageal gastrostomy/jejunostomy (PTEG/J) as a viable alternative to nasogastric decompression in patients who are not candidates for PEG/J. PTEG/J is a largely unknown technique in the United States that designed to gain access to the stomach and proximal small bowel in these patients. We describe the use of PTEG/J in 3 patients with metastatic gastric cancer by using resources and techniques readily available in a well-stocked interventional radiology suite. PATIENTS: In the first case, percutaneous transesophageal gastrostomy (PTEG) was placed for palliation of intractable nausea and vomiting in a 37-year-woman with diffuse gastric cancer and peritoneal carcinomatosis. In the second case, PTEG was extended into the jejunum for feeding a 60-year-old woman with metastatic gastric cancer. In the third case, PTEG extending into the jejunum was placed in a 69-year-old man for palliation of bowel obstruction caused by metastatic gastric cancer and peritoneal carcinomatosis. METHODS: After adequate sedation is administered, a 22 x 4-mm balloon catheter is passed into the esophagus over a guidewire just below the thoracic inlet. The balloon is ruptured with a needle passed through the neck under US guidance. A guidewire is then passed through the needle into the balloon and carried into the stomach or proximal small bowel by advancing the balloon catheter. The track is then dilated over the guidewire and a pigtail 45-cm-long 14F nephrostomy tube then passed into the stomach or into the proximal small bowel over the guidewire. The catheter is secured by suturing to the skin of the neck. RESULTS: PTEG/J was effective in achieving palliation or feeding in our patients. No complications occurred. CONCLUSIONS: PTEG/J is a safe and effective alternative to standard percutaneous gastrostomy/jejunostomy tube placement for decompression of bowel obstruction or feeding in appropriately selected patients.