Indexado en

Licencia y uso

Citaciones

Cited 60 times in

Cited 45 times in

Altmetrics

Grant support

This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades, under the following projects: Project MAT2017-88148-R, SAF-2017-82223-R, PIE-201760E007, and Nanobioap cluster of excellence under project MAT2016-81955-REDT. Portilla received a predoctoral FPU grant (FPU15/06170) from the same Ministry. S.D.S.-F. acknowledges the economic support by CONACyT and Institute Politecnico Nacional SIP 20180252 (Mexico). The authors thank the CNB confocal microscopy facility, the CNB flow cytometry facility, and CNB TEM facility for their technical support. L.G. acknowledges financial support from the Ramon y Cajal subprogram (RYC-2014-15512). The authors would like to acknowledge the Advanced Microscopy Laboratory (INA-Universidad de Zaragoza) for access to their instrumentation and expertise.

Análisis de autorías institucional

Compartir

Flower-like Mn-Doped Magnetic Nanoparticles Functionalized with alpha(v)beta(3)-Integrin-Ligand to Efficiently Induce Intracellular Heat after Alternating Magnetic Field Exposition, Triggering Glioma Cell Death

Publicado en:ACS Applied Materials & Interfaces. 11 (30): 26648-26663 - 2019-07-31 11(30), DOI: 10.1021/acsami.9b08318

Autores: Del Sol-Fernandez, S.; Portilla-Tundidor, Y.; Gutierrez, L.; Odio, O. F.; Reguera, E.; Barber, D. F.; Morales, M. P.;

Afiliaciones

Resumen

Despite the potential of magnetic nanoparticles (NPs) to mediate intracellular hyperthermia when exposed to an alternating magnetic field (AMF), several studies indicate that the intracellular heating capacity of magnetic NPs depends on factors such as cytoplasm viscosity, nanoparticle aggregation within subcellular compartments, and dipolar interactions. In this work, we report the design and synthesis of monodispersed flowerlike superparamagnetic manganese iron oxide NPs with maximized SAR (specific absorption rate) and evaluate their efficacy as intracellular heaters in the human tumor-derived glioblastoma cell line U87MG. Three main strategies to tune the particle anisotropy of the core and the surface to reach the maximum heating efficiency were adopted: (1) varying the crystalline anisotropy by inserting a low amount of Mn2+ in the inverse spinel structure, (2) varying the NP shape to add an additional anisotropy source while keeping the superparamagnetic behavior, and (3) maximizing NP-cell affinity through conjugation with a biological targeting molecule to reach the NP concentration required to increase the temperature within the cell. We investigate possible effects produced by these improved NPs under the AMF (f = 96 kHz, H = 47 kA/m) exposure in the glioblastoma cell line U87MG by monitoring the expression of hsp70 gene and reactive oxygen species (ROS) production, as both effects have been described to be induced by increasing the intracellular temperature. The induced cell responses include cellular membrane permeabilization and rupture with concomitant high ROS appearance and hsp70 expression, followed by cell death. The responses were largely limited to cells that contained the NPs exposed to the AMF. Our results indicate that the developed strategies to optimize particle anisotropy in this work are a promising guidance to improve the heating efficiency of magnetic NPs in the human glioma cell line.

Palabras clave