Local Temperature Increments and Induced Cell Death in Intracellular Magnetic Hyperthermia

resumo

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 gamma-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 degrees 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.

palavras-chave

NANOPARTICLE HYPERTHERMIA; MOLECULAR THERMOMETER; PROSTATE-CANCER; THERMOTHERAPY; THERMOREGULATION; MITOCHONDRIA; FEASIBILITY; RESPONSES; LIFE

categoria

Chemistry; Science & Technology - Other Topics; Materials Science

autores

Gu, YY; Piñol, R; Moreno-Loshuertos, R; Brites, CDS; Zeler, J; Martínez, A; Maurin-Pasturel, G; Fernández-Silva, P; Marco-Brualla, J; Téllez, P; Cases, R; Belsué, RN; Bonvin, D; Carlos, LD; Millán, A

Grupos

G2 - Materiais Fotónicos, Eletrónicos e Magnéticos

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

The shape of water: Nanothermometry as a tool to unveil the structure of liquid water and water-based nanofluids (THE SHAPE OF WATER )

Nanoparticles - based 2D thermal bioimaging technologies - NanoTBTech (NanoTBTech)

agradecimentos

This work was supported by the Spanish Ministry of Science Innovation and Universities [Grants Nos. PGC2018_095795_B_I00 and PID2021-124354NB-I00] and the Diputacion General de Aragon [Grants Nos. LMP220_21 and E11/17R]. It is also developed within the scope of the projects CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020, and Shape of Water (PTDC/NAN-PRO/3881/2020) financed by Portuguese funds through the FCT/MEC (PIDDAC). The support of the European Union's Horizon 2020 FET Open program under grant agreement numbers 801305 (Nano-TBTech) and 829162 (Hotzymes) is also acknowledged. The authors would like to acknowledge the use of the Servicio General de Apoyo a la Investigacion-SAI, University of Zaragoza.