Non-invasive monitoring of branched Au nanoparticle-mediated photothermal ablation.

Nanoparticle-mediated photothermal therapy for treatment of different types of tumors has attracted tremendous attention in recent years. One major factor that drives this therapy is the ability to carefully control and prevent inadvertent damage to local tissues, while focusing therapeutic heating to specific regions of the tumor tissues. To this end, it is critical to generate efficient heating in the targeted tumors while monitoring the extent and distribution of heating. In our study, we demonstrated the photothermal heating properties of our synthesized branched Au nanoparticles (b-AuNPs) using non-invasive MR thermometry (MRT) techniques to assess its effects both in vitro and in vivo. 75 nm b-AuNPs were synthesized; these b-AuNPs demonstrated strong near infrared (NIR) absorption and high heat transducing efficiency. Proton resonance frequency MRT approaches for monitoring b-AuNPs mediated heating were validated using in vitro agar phantoms and further evaluated during in vivo animal model tumor ablation studies. In vitro phantom studies demonstrated a strong linear correlation between MRT and reference-standard thermocouple measurements of b-AuNPs-mediated heating upon NIR laser irradiation; temperatures increased with both an increase in laser power and increased exposure duration. Localized photothermal heating in regions containing the b-AuNPs was confirmed through MRT generated temperature maps acquired serially at increasing depths during both phantom and in vivo studies. Our results suggested that b-AuNPs exposed to NIR radiation produced highly efficient localized heating that can be accurately monitored dynamically using non-invasive MRT measurements. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2352-2359, 2017.

Temperature-sensitive magnetic drug carriers for concurrent gemcitabine chemohyperthermia.

To improve the efficacy of gemcitabine (GEM) for the treatment of advanced pancreatic cancer via local hyperthermia potentiated via a multi-functional nanoplatform permitting both in vivo heating and drug delivery is the goal of this study. Here, a chemohyperthermia approach to synergistically achieve high intra-tumoral drug concentrations, while permitting concurrent hyperthermia for more effective tumor cell kill and growth inhibition, is proposed. Drug delivery and hyperthermia are achieved using a hydroxypropyl cellulose (HPC)-grafted porous magnetic drug carrier that is MRI visible to permit in vivo visualization of the biodistribution. These synthesized magnetic drug carriers produce strong T2 -weighted image contrast and permit efficient heating using low-magnetic-field intensities. The thermomechanical response of HPC permits triggered GEM release confirmed during in vitro drug release studies. During in vitro studies, pancreatic cancer cell growth is significantly inhibited (≈82% reduction) with chemohyperthermia compared to chemotherapy or hyperthermia alone. Using PANC-1 xenografts in nude mice, the delivery of injected GEM-loaded magnetic carriers (GEM-magnetic carriers) is visualized with both MRI and fluorescent imaging techniques. Chemohyperthermia with intra-tumoral injections of GEM-magnetic carriers (followed by heating) results in significant increases in apoptotic cell death compared to tumors treated with GEM-magnetic carriers injections alone. Chemohyperthermia with GEM-magnetic carriers offers the potential to significantly improve the therapeutic efficacy of GEM for the treatment of pancreatic cancer. In vivo delivery confirmation with non-invasive imaging techniques could permit patient-specific adjustments therapeutic regimens for improve longitudinal outcomes.

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

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.