Díaz-Riascos Zamira V, Llaguno-Munive Monserrat, Lafuente-Gómez Nuria, Luengo Yurena, Holmes Sarah, Volatron Jeanne, Ibarrola Oihane, Mancilla Sandra, Sarno Francesca, Aguirre José Javier, Razafindrakoto Sarah, Southern Paul, Terán Francisco J, Keogh Anna, Salas Gorka, Prina-Mello Adriele, Lacal Juan Carlos, Del Pozo Angel, Pankhurst Quentin A, Hidalgo Manuel, Gazeau Florence, Somoza Álvaro, Schwartz Simó, Abasolo Ibane
Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT), Vall d'Hebron Institute of Research (VHIR), 08035 Barcelona, Spain.
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 08035 Barcelona, Spain.
ACS Appl Mater Interfaces. 2025 Jan 15;17(2):2924-2939. doi: 10.1021/acsami.4c16129. Epub 2025 Jan 2.
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. cell viability assays show that the combination of low doses of CT and HT is highly synergistic, particularly in the BxPC-3 cell line. , 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.
胰腺导管腺癌（PDAC）是一种极具挑战性的疾病，预后很差。其特征是存在致密的促纤维增生性基质，这会阻碍药物渗透并限制传统化疗（CT）的疗效。作为一种替代方案，CT与热疗（HT）联合已被提议作为PDAC的一种创新治疗方式。在之前的研究中，我们报道了氧化铁磁性纳米颗粒（MNPs）的研发情况，当这些纳米颗粒暴露于时变磁场时，会表现出强烈的热疗反应，从而抑制胰腺癌的生长。我们在此报告这些MNPs作为瘤内注射无菌磁流体（“NoCanTher热疗”或“NTT”制剂）与静脉注射标准护理药物（吉西他滨和纳米白蛋白结合型紫杉醇）联合用于治疗PDAC在临床应用方面取得的进展。细胞活力测定表明，低剂量CT与HT联合具有高度协同作用，尤其是在BxPC - 3细胞系中。此外，生物分布测定表明，NTT制剂MNPs主要保留在肿瘤内，集中在基质成分高的区域周围。而且，联合CT/HT治疗在药物渗透和肿瘤体积缩小方面比单纯CT治疗具有明显优势，这表明HT可能直接作用于破坏间质基质，以促进药物进入恶性细胞。这些研究已促使西班牙巴塞罗那的比埃斯堡大学医院批准并启动了一项针对局部晚期PDAC患者的临床研究，研究NTT制剂与CT联合使用的情况。
