Nanoparticle Heating
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Nanoparticle Heating - 1

Hybrid gold-iron oxide nanoparticles have been shown to hold great potential for heat triggered drug delivery1,2. The magnetic core of the particles enables magnetic resonance imaging whilst the gold surface coating can act as a localised heat source after laser irradiation by exploitation of the surface plasmon resonance. Earlier work had reported heating properties in agar3, inside cells4 and in tumour bearing xenograft cadavers4 after irradiation with a 1064 nm laser source. The purpose of this work was to test whether the Chromacity 1040 nm was A) useful for laser irradiation of these nanoparticles and B) more effective than the previous laser source. Methodology Agar phantoms Hybrid nanoparticles were suspended in 2% agar phantoms at 5 fjgml-1 and 50 fjgml-1. The gels were irradiated for 60 seconds using the Chromacity 1040 nm and changes in heat monitored using an Optris PI640 thermal imaging camera (Optris, Germany). The subsequent 60 seconds following irradiation was also monitored to understand the cooling profile of the particles. Heat dissipation was deduced from the infrared images up to 12 mm from the point of irradiation. All reported thermal change is in respect to a control agar phantom containing no nanoparticles. In vitro Human pancreatic adenocarcinoma (BxPC-3) cells were seeded into 6-well plates (50,000 cells/ well) containing quartz coverslips (Alfa Aesar, USA) and incubated at 37 °C with 5 % CO2. Hybrid nanoparticles (5 fjgml-1 & 50 fjgml-1) were incubated with the cells for 24 hrs. Cells were washed with phosphate buffered saline (PBS) four times and the coverslips removed from the plate. The cells were irradiated using the Chromacity 1040 nm for 60 seconds or 4 repetitions of 60 seconds with a 60 seconds cooling period between. After irradiation the coverslips were returned to the 6 well plate, fresh media added and incubated for 24 hrs. After this time, the cytotoxicity was measured using trypan blue exclusion as previously described. Cytotoxicity was measured in relation to control cells with no nanoparticles. In vivo Female Nu/Nu mice, five weeks of age (n=3), (Charles River, UK) were kept in pathogen-free conditions (weight of mice was 20-25 g). Human pancreatic cancer cell line BxPC-3 was cultured to 90 % confluence in RPMI 1640 supplemented with 10 % fetal bovine serum and 1 % penicillin streptomycin. The cells were washed twice with cold PBS and harvested with trypsin for 10 min at 37 °C. The cells were washed three times with PBS and resuspended in 50:50 media:PBS. The tumour cell suspension (3.0 * 106 cells in 100 fjl of 50:50 PBS:media) was injected subcutaneously (s.c.) in the right flank of each mouse. When the tumour became palpable (approximately after one week), measurements in two dimensions with Vernier callipers were carried out twice a week and the volume of the tumours calculated according to Equation 1. The aim of this experiment was to test if the Chromacity 1040 was A) useful for laser irradiation of these nanoparticles and B) more effective than the previous laser source. sales@chromacitylasers.com Version 2 © Chromacity Ltd - 2020 Discover More chromacitylasers.com

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Nanoparticle Heating - 2

Heating of Hybrid Gold-Iron Oxide Nanoparticles in Biological Media -6 -3 0 3 6 Distance from irradiation point, mm FIGURE 1. Infrared monitoring of hybrid nanoparticles in 2% agar after 60 s irradiation with the Chromacity 1040 nm showing A) Thermal change over 120 s and B) Heat dissipation from laser source at 60 s irradiation (n=3,±SD). Once tumour volume reached a maximum of 0.9 cm3 the mice were sacrificed and used for imaging immediately post mortem. Hybrid nanoparticle solution (0.2 mgkg-1 or 0.02 mgkg-1 100 μl) was injected intra-tumorally (I.T.) using a 26 gauge needle (Vet-Tech,...

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Nanoparticle Heating - 3

Heating of Hybrid Gold-Iron Oxide Nanoparticles in Biological Media using the Chromacity 1040 Time, Seconds Distance from irradiation point, mm Figure 4. Infared monitoring of hybrid nanoparticles in tumor bearing nude mouse xenographs cadavers after 60 s irradiation with the Chromacity laser source showing A) Thermal change over 120 s and B) Heat dissipation from laser source at 60 s irradiation (n=3,±SD). Thermal rise and heat dissipation was measured in a xenograft bearing cadaver. The hybrid particles were injected intra-tumorally at the equivalent concentrations dependant on mouse...

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