Hematological results from primary blood samples (n = 10) that were used to derive blood preparations.

<p>Hematological results from primary blood samples (n = 10) that were used to derive blood preparations.</p

Coefficients of multivariate regression models for mtDNAcn(WB) measured in blood preparations (n = 46).

<p>Coefficients of multivariate regression models for mtDNAcn(WB) measured in blood preparations (n = 46).</p

Hematological results from primary blood samples (n = 10) that were used to derive blood preparations.

<p>Hematological results from primary blood samples (n = 10) that were used to derive blood preparations.</p

Scatter plot of the change of mtDNAcn(WB) per unit increase of the platelets/leukocyte ratio.

<p>This scatter plot shows the change of mtDNAcn(WB) per unit increase of the platelets/leukocyte ratio. Data from 46 preparations are shown. Individual mtDNAcn(WB) for each preparation are plotted as white circles. The line represents the fit of a linear model (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163770#pone.0163770.t003" target="_blank">Table 3</a>, Model 6). mtDNAcn(WB): mitochondrial DNA copy number measured in whole blood.</p

Platelet count, Leukocyte count and mtDNAcn(WB) distributions in all subjects from the AWHS cohort study (n = 3389).

<p>Platelet count, Leukocyte count and mtDNAcn(WB) distributions in all subjects from the AWHS cohort study (n = 3389).</p

Local Temperature Increments and Induced Cell Death in Intracellular Magnetic Hyperthermia

The generation of temperature gradients on nanoparticles heated externally by a magnetic field is crucially important in magnetic hyperthermia therapy. But the intrinsic low heating power of magnetic nanoparticles, at the conditions allowed for human use, is a limitation that restricts the general implementation of the technique. A promising alternative is local intracellular hyperthermia, whereby cell death (by apoptosis, necroptosis, or other mechanisms) is attained by small amounts of heat generated at thermosensitive intracellular sites. However, the few experiments conducted on the temperature determination of magnetic nanoparticles have found temperature increments that are much higher than the theoretical predictions, thus supporting the local hyperthermia hypothesis. Reliable intracellular temperature measurements are needed to get an accurate picture and resolve the discrepancy. In this paper, we report the real-time variation of the local temperature on γ-Fe2O3 magnetic nanoheaters using a Sm3+/Eu3+ ratiometric luminescent thermometer located on its surface during exposure to an external alternating magnetic field. We measure maximum temperature increments of 8 °C on the surface of the nanoheaters without any appreciable temperature increase on the cell membrane. Even with magnetic fields whose frequency and intensity are still well within health safety limits, these local temperature increments are sufficient to produce a small but noticeable cell death, which is enhanced considerably as the magnetic field intensity is increased to the maximum level tolerated for human use, consequently demonstrating the feasibility of local hyperthermia