Photothermal ablation of pancreatic cancer cells with hybrid iron-oxide core gold-shell nanoparticles

Abstract

Yang Guo,1 Zhuoli Zhang,1 Dong-Hyun Kim,1,5 Weiguo Li,1 Jodi Nicolai,1 Daniel Procissi,1 Yi Huan,2 Guohong Han,3 Reed A Omary,1,4,5 Andrew C Larson1,4,5 1Department of Radiology, Northwestern University, Chicago, IL, USA; 2Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China; 3Department of Digestive Interventional Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China; 4Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA Purpose: Photothermal ablation is a minimally invasive approach, which typically involves delivery of photothermal sensitizers to targeted tissues. The purpose of our study was to demonstrate that gold nanoparticles are phagocytosed by pancreatic cancer cells, thus permitting magnetic resonance imaging (MRI) of sensitizer delivery and photothermal ablation. Patients and methods: Iron-oxide core/gold-shell nanoparticles (GoldMag®, 30 nm diameter; Xi'an GoldMag Biotechnology Co, Xi'an, People's Republic of China) were used. In a 96-well plate, 3 × 104 PANC-1 (human pancreatic cancer cell line) cells were placed. GoldMag (0, 25, or 50 µg/mL) was added to each well and 24 hours allowed for cellular uptake. Samples were then divided into two groups: one treated with photothermal ablation (7.9 W/cm2) for 5 minutes, the other not treated. Photothermal ablation was performed using laser system (BWF5; B&W Tek, Inc, Newark, DE, USA). Intraprocedural temperature changes were measured using a fiber optic temperature probe (FTP-LN2; Photon Control Inc, Burnaby, BC, Canada). After 24 hours, the remaining number of viable cells was counted using trypan blue staining; cell proliferation percentage was calculated based on the total number of viable cells after treatment compared with control. MRI of GoldMag uptake was performed using a 7.0T ClinScan system (Bruker BioSpin, Ettlingen, Germany). Results: Temperature curves demonstrated that with increased GoldMag uptake, laser irradiation produced higher temperature elevations in the corresponding samples; temperature elevations of 12.89°C, 35.16°C, and 79.51°C were achieved for 0, 25, and 50 µg/mL GoldMag. Without photothermal ablation, the cell proliferation percentage changed from 100% to 71.3% and 47.0% for cells treated with 25 and 50 µg/mL GoldMag. Photothermal ablation of PANC-1 cells demonstrated an effective treatment response, specifically a reduction to only 61%, 21.9%, and 2.3% cell proliferation for cells treated with 0, 25, and 50 µg/mL GoldMag. MRI was able to visualize GoldMag uptake within PANC-1 cells. Conclusion: Our findings suggest that photothermal ablation may be effective in the treatment of pancreatic cancer. GoldMag nanoparticles could serve as photothermal sensitizers, and MRI is feasible to quantify delivery. Keywords: photothermal ablation therapy, hybrid nanoparticles, magnetic resonance imaging