Flower-like Mn-Doped Magnetic Nanoparticles Functionalized with αvβ3-Integrin-Ligand to Efficiently Induce Intracellular Heat after Alternating Magnetic Field Exposition, Triggering Glioma Cell Death

S. Del Sol-Fernández, Y. Portilla-Tundidor, L. Gutiérrez, O. F. Odio, E. Reguera, D. F. Barber, M. P. Morales

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)26648-26663
Number of pages16
JournalACS Applied Materials and Interfaces
Volume11
Issue number30
DOIs
StatePublished - 31 Jul 2019
Externally publishedYes

Keywords

  • biological responses to heat
  • cell death
  • intracellular hyperthermia
  • manganese iron oxide nanoparticles
  • optimized uptake
  • oxidative stress

Fingerprint

Dive into the research topics of 'Flower-like Mn-Doped Magnetic Nanoparticles Functionalized with αvβ3-Integrin-Ligand to Efficiently Induce Intracellular Heat after Alternating Magnetic Field Exposition, Triggering Glioma Cell Death'. Together they form a unique fingerprint.

Cite this