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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.

Analysis of institutional authors

Portilla Tundidor, YadileinyAuthor

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Article

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

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

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

Affiliations

CIBER BBN, Zaragoza 50009, Spain - Author
CSIC, CNB, Dept Immunol & Oncol & Nanobiomed Initiat, Darwin 3, Madrid 28049, Spain - Author
CSIC, ICMM, Dept Energy Environm & Hlth, Sor Juana Ines de la Cruz 3, Madrid 28049, Spain - Author
Inst Politecn Nacl, Ctr Invest Ciencia Aplicada & Tecnol Avanzada, Unidad Legaria CICATA Legaria, Calz Legaria 694,Col Irrigac, Mexico City 11500, DF, Mexico - Author
Univ Zaragoza, CSIC, ICMA, Inst Nanociencia Aragon,Dept Quim Analit, E-50009 Zaragoza, Spain - Author
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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.

Keywords

biological responses to heatcell deathintracellular hyperthermiamanganese iron oxide nanoparticlesoptimized uptakeBiological responses to heatCell deathEndocytosisExpressionFe3o4 nanoparticlesGenerationHyperthermiaIn-vitroIntegrinIntracellular hyperthermiaIron-oxide nanoparticlesManganese iron oxide nanoparticlesNanoflowersOptimized uptakeOxidative stressToxicity

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal ACS Applied Materials & Interfaces due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 33/314, thus managing to position itself as a Q1 (Primer Cuartil), in the category Materials Science, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.86. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 5.36 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 6.06 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-29, the following number of citations:

  • WoS: 45
  • Scopus: 60

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-29:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 98.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 98 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.85.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Mexico.