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Domingo-Diez, JavierAuthorCasanova-Carvajal, OscarAuthorMarrodan, LorenaAuthorSerrano-Olmedo, Jose-JavierAuthorRamos-Gomez, MilagrosCorresponding Author

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August 7, 2025
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Effect of Photothermal Therapy Using Gold Nanoparticles Conjugated with Hyaluronic Acid in an Intracranial Murine Glioblastoma Model

Publicated to: International Journal of Nanomedicine. 20 9327-9346 - 2025-01-01 20(), DOI: 10.2147/ijn.s525462

Authors:

Domingo-Diez, Javier; Foti, Alice; Casanova-Carvajal, Oscar; Marrodan, Lorena; Granado, Noelia; Satriano, Cristina; Martinez-Murillo, Ricardo; Serrano-Olmedo, Jose-Javier; Ramos-Gomez, Milagros
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Affiliations

CSIC, Inst Cajal, Dept Translat Neurosci, Neurovasc Res Grp, Madrid 28002, Spain - Author
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Madrid 28029, Spain - Author
Univ Catania, Dept Chem Sci, Nano Hybrid Biointerfaces Lab NHBIL, I-95125 Catania, Italy - Author
Univ Politecn Madrid UPM, Ctr Biomed Technol CTB, Madrid 28223, Spain - Author
Univ Politecn Madrid, Dept Tecnol Foton & Bioingn, ETSI Telecomunicac, Madrid 28040, Spain - Author
Univ Politecn Madrid, Escuela Tecn Super Ingn & Diseno Ind ETSIDI, Dept Ingn Elect Elect Automat & Fis Aplicada, Madrid 28012, Spain - Author
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Abstract

Purpose: Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor. Conventional treatments for GBM include surgery, chemotherapy, radiotherapy, or a combination of these. However, emerging therapies, such as hyperthermia treatments, are being developed. One of these new therapies is nanoparticle-mediated photothermal therapy (PTT), a non-invasive treatment that converts light into heat using photoagents such as plasmonic nanoparticles. High molecular weight hyaluronic acid (HA) has been described as a potential inhibitor of tumor progression and exhibits a high affinity for the CD44 receptor, which is present in GBM cells. The in vivo efficacy of gold nanorods (GNRs) biofunctionalized with HA-700kDa in PTT has been evaluated in a murine Animals and Methods: Adult male C57/BL-6 mice (N=15), 3-8-month-old, were used for PTT experiments. CT2A cells were injected into the mouse brain to establish a GBM model. Tumor-bearing mice were randomly divided into three groups: Control (untreated, n=5), GNRs (injected with GNRs, n=5) and PTT-treated (injected with GNRs and treated with laser, n=5). After GNR injection, mice were irradiated with a laser at 0.98 A (250mW) for 25 min over three consecutive days. Results: As observed in the analysis of tumor sizes from all MR images, animals treated with a laser following GNR injection exhibited significantly smaller tumor sizes compared to control and GNR-treated animals one week after the treatment. In addition, PTT treatment led to a notable improvement in the exploratory behavior of the treated animals and an increase in their life expectancy compared to untreated control mice. Conclusion: This study demonstrates the efficacy of GNR-based-PTT, applied to an orthotopic tumor model, using GNRs biofunctionalized with HA to target GBM CT2A cells. The treatment resulted in a reduction in tumor mass and an extension of life expectancy in GNR-PTT treated mice.
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Keywords

AnimalsBiologyBrain neoplasmsCd4Cell line, tumorCellsCentral-nervous-systemCytotoxicityDisease models, animalGlioblastomaGoldGold nanorodsHyaluronic acidInductionMaleMetal nanoparticlesMiceMice, inbred c57blMurine tumor modeMurine tumor modelNanorodsNanotubesPhotothermal therapySize

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal International Journal of Nanomedicine 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, 2025, it was in position 28/352, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-25:

  • Google Scholar: 5
  • WoS: 7
  • Scopus: 7
  • Europe PMC: 4
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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 2026-04-25:

  • 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: 6 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://oa.upm.es/93688/

As a result of the publication of the work in the institutional repository, statistical usage data has been obtained that reflects its impact. In terms of dissemination, we can state that, as of

  • Views: 28
  • Downloads: 15
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Leadership analysis of institutional authors

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

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (DOMINGO DIEZ, JAVIER) and Last Author (RAMOS GOMEZ, MARIA MILAGROS).

the author responsible for correspondence tasks has been RAMOS GOMEZ, MARIA MILAGROS.

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Project objectives

Los objetivos perseguidos en esta aportación se centran en evaluar la eficacia de la terapia fototérmica mediada por nanopartículas de oro conjugadas con ácido hialurónico en un modelo murino de glioblastoma intracraneal. Se pretende analizar la capacidad de los nanorods de oro biofuncionalizados con HA-700kDa para reducir el tamaño tumoral tras la irradiación con láser. Además, se busca determinar el impacto de esta terapia en el comportamiento exploratorio de los animales tratados. Otro objetivo es evaluar la extensión de la esperanza de vida en ratones con glioblastoma tras el tratamiento con PTT. Finalmente, se pretende validar el uso de ácido hialurónico para dirigir selectivamente la terapia hacia células tumorales CD44 positivas.
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Most relevant results

Los resultados más relevantes del estudio evidencian la eficacia de la terapia fototérmica mediada por nanorods de oro conjugados con ácido hialurónico (HA-700kDa) en un modelo murino intracraneal de glioblastoma. En primer lugar, los animales tratados con terapia fototérmica (PTT) mostraron tamaños tumorales significativamente menores en imágenes de resonancia magnética una semana tras el tratamiento en comparación con los grupos control y solo con GNRs. En segundo lugar, el tratamiento PTT mejoró notablemente el comportamiento exploratorio de los animales tratados. Finalmente, se observó un aumento en la esperanza de vida de los ratones sometidos a PTT frente a los controles no tratados, confirmando la eficacia del tratamiento en la reducción de masa tumoral y extensión de supervivencia.
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Awards linked to the item

The authors would like to thank Soledad Martinez for the excellent technical assistance. This study was partially funded by the Ministerio de Ciencia, Innovacion y Universidades of Spain, Refs.: PGC2018-097531-B-I00, PID2022-138881OB-I00 and PDC2022-133028-I00, funded by the European Union-NextGenerationEU. CS acknowledges the financial supported by MUR in the framework of PRIN2022-PNRR call under project CoMu4CaT. The abstract of this paper was presented at the 7th Spanish Conference on Biomedical Applications of Nanomaterials (SBAN) .
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Contextual narrative

Este artículo representa una continuación natural y una profundización significativa de mi línea de investigación previa en terapias fototérmicas para glioblastoma, anteriormente demostrada en nuestro estudio sobre el enlentecimiento del crecimiento tumoral mediante hipertermia óptica con nanorods de oro en el modelo CT‑2A. En esta nueva publicación amplío ese enfoque inicial incorporando nanopartículas de oro biofuncionalizadas con ácido hialurónico (HA‑700 kDa), lo que permite dirigir de manera más eficiente la terapia hacia células glioblastoma que sobreexpresan el receptor CD44. Este avance no solo refina la estrategia terapéutica, sino que la hace más específica, biológicamente relevante y potencialmente más trasladable a entornos clínicos. 

Como coautor, participé en el diseño del estudio in vivo, donde se demostró que la fototermia mediada por estas nanopartículas combinada con irradiación láser controlada produce una reducción tumoral significativamente mayor que en los controles y una mejoría notable en el comportamiento exploratorio y la esperanza de vida de los animales tratados. Estos resultados consolidan y amplían los hallazgos de mi trabajo previo, evidenciando que la integración de biofuncionalización con HA aporta un salto cualitativo en la eficacia de la terapia fototérmica. Así, este artículo profundiza en los mecanismos, optimiza la estrategia y reafirma el potencial de las nanopartículas de oro como plataforma terapéutica avanzada frente al glioblastoma.

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