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Preclinical Development of Magnetic Nanoparticles for Hyperthermia Treatment of Pancreatic Cancer

Díaz-Riascos, Zamira V; Llaguno-Munive, Monserrat; Lafuente-Gómez, Nuria; Luengo, Yurena; Holmes, Sarah; Volatron, Jeanne; Ibarrola, Oihane; ... Abasolo, Ibane; + view all (2025) Preclinical Development of Magnetic Nanoparticles for Hyperthermia Treatment of Pancreatic Cancer. ACS Applied Materials & Interfaces , 17 (2) pp. 2924-2939. 10.1021/acsami.4c16129.

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a very challenging disease with a very poor prognosis. It is characterized by a dense desmoplastic stroma that hampers drug penetration and limits the effectiveness of conventional chemotherapy (CT). As an alternative, the combination of CT with hyperthermia (HT) has been proposed as an innovative treatment modality for PDAC. In previous works, we reported on the development of iron oxide magnetic nanoparticles (MNPs) that, when exposed to time-varying magnetic fields, exhibit strong HT responses that inhibited the growth of pancreatic cancers. We report here on advances toward the clinical use of these MNPs as an intratumorally administered sterile magnetic fluid (the "NoCanTher ThermoTherapy" or "NTT" Agent) alongside intravenous standard-of-care drugs (gemcitabine and nab-paclitaxel) for the treatment of PDAC. In vitro cell viability assays show that the combination of low doses of CT and HT is highly synergistic, particularly in the BxPC-3 cell line. In vivo, biodistribution assays showed that the NTT Agent MNPs remained mainly within the tumor, concentrated around areas with a high stromal component. Moreover, the combined CT/HT treatment shows clear advantages over CT alone in terms of drug penetration and reduction of the tumor volume, suggesting a potential direct effect of HT in the disruption of the interstitial stroma to facilitate the access of the drugs to malignant cells. These studies have led to the approval and commencement of a clinical investigational study at the Vall d'Hebron University Hospital (Barcelona, Spain) of the NTT Agent alongside CT in patients with locally advanced PDAC.

Type: Article
Title: Preclinical Development of Magnetic Nanoparticles for Hyperthermia Treatment of Pancreatic Cancer
Location: United States
DOI: 10.1021/acsami.4c16129
Publisher version: https://doi.org/10.1021/acsami.4c16129
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: alternating magnetic field, chemotherapy, combination therapy, hyperthermia, iron oxide nanoparticles, nanoparticle biodistribution, pancreatic cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10204715
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