Determining iron oxide nanoparticle heating efficiency and elucidating local nanoparticle temperature for application in agarose gel-based tumor model.

Magnetic iron oxide nanoparticles (MNPs) have been developed for magnetic fluid hyperthermia (MFH) cancer therapy, where cancer cells are treated through the heat generated by application of a high frequency magnetic field. This heat has also been proposed as a mechanism to trigger release of chemotherapy agents. In each of these cases, MNPs with optimal heating performance can be used to maximize therapeutic effect while minimizing the required dosage of MNPs. In this study, the heating efficiencies (or specific absorption rate, SAR) of two types of MNPs were evaluated experimentally and then predicted from their magnetic properties. MNPs were also incorporated in the core of poly(ethylene glycol-b-caprolactone) micelles, co-localized with rhodamine B fluorescent dye attached to polycaprolactone to monitor local, nanoscale temperatures during magnetic heating. Despite a relatively high SAR produced by these MNPs, no significant temperature rise beyond that observed in the bulk solution was measured by fluorescence in the core of the magnetic micelles. MNPs were also incorporated into a macro-scale agarose gel system that mimicked a tumor targeted by MNPs and surrounded by healthy tissues. The agarose-based tumor models showed that targeted MNPs can reach hyperthermia temperatures inside a tumor with a sufficient MNP concentration, while causing minimal temperature rise in the healthy tissue surrounding the tumor.

Evaluating the toxicity of bDtBPP on CHO-K1 cells for testing of single-use bioprocessing systems considering media selection, cell culture volume, mixing, and exposure duration.

Single-use bioprocessing bags are gaining popularity due to ease of use, lower risk of contamination, and ease of process scale-up. Bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP), a degradant of tris(2,4-di-tert-butylphenyl)phosphite, marketed as Irgafos 168®, which is an antioxidant stabilizer added to resins, has been identified as a potentially toxic leachate which may impact the performance of single-use, multilayer bioprocessing bags. In this study, the toxicity of bDtBPP was tested on CHO-K1 cells grown as adherent or suspended cells. The EC50 (effective concentration to cause 50% cell death) for adherent cells was found to be one order of magnitude higher than that for suspended CHO-K1 cells. While CHO-K1 cells had good cell viability when exposed to moderate concentrations of bDtBPP, the degradant was shown to impact the viable cell density (VCD) at much lower concentrations. Hence, in developing an industry-standard assay for testing the cytotoxicity of leachates, suspended cells (as commonly used in the bioprocessing industry) would likely be most sensitive, particularly when reporting EC50 values based on VCD. The effects of mixing, cell culture volume, and exposure duration were also evaluated for suspended CHO-K1 cells. It was found that the sensitivity of cell culture to leachates from single-use plastic bags was enhanced for suspended cells cultured for longer exposure times and when the cells were subjected to continuous agitation, both of which are important considerations in the production of biopharmaceuticals. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1318-1323, 2016.

Impact of magnetic field parameters and iron oxide nanoparticle properties on heat generation for use in magnetic hyperthermia.

Heating of nanoparticles (NPs) using an AC magnetic field depends on several factors, and optimization of these parameters can improve the efficiency of heat generation for effective cancer therapy while administering a low NP treatment dose. This study investigated magnetic field strength and frequency, NP size, NP concentration, and solution viscosity as important parameters that impact the heating efficiency of iron oxide NPs with magnetite (Fe3O4) and maghemite (γ-Fe2O3) crystal structures. Heating efficiencies were determined for each experimental setting, with specific absorption rates (SARs) ranging from 3.7 to 325.9 W/g Fe. Magnetic heating was conducted on iron oxide NPs synthesized in our laboratories (with average core sizes of 8, 11, 13, and 18 nm), as well as commercially-available iron oxides (with average core sizes of 8, 9, and 16 nm). The experimental magnetic coil system made it possible to isolate the effect of magnetic field parameters and independently study the effect on heat generation. The highest SAR values were found for the 18 nm synthesized particles and the maghemite nanopowder. Magnetic field strengths were applied in the range of 15.1 to 47.7 kA/m, with field frequencies ranging from 123 to 430 kHz. The best heating was observed for the highest field strengths and frequencies tested, with results following trends predicted by the Rosensweig equation. An increase in solution viscosity led to lower heating rates in nanoparticle solutions, which can have significant implications for the application of magnetic fluid hyperthermia in vivo.