New pancreatic cancer treatment boosts pancreatic cancer defences and slows tumour growth in mice
Magnetic hyperthermia is an experimental anti-tumour treatment that could be useful for pancreatic cancer. It involves the use of magnetic nanoparticles that generate heat when exposed to an external magnetic field that is harmless to tissues. To advance in this line, researchers from the Instituto de Nanociencia y Materiales de Aragón (INMA), a joint centre of the Consejo Superior de Investigaciones Científicas (CSIC) and the University of Zaragoza, and the CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), have studied several critical parameters in its effectiveness, and have detected an increase in the immune response in animal models and a greater inhibition of tumour growth.
In this work, published in the journal ACS Applied Materials and Interfaces, they studied the effect of magnetic hyperthermia in pancreatic cancer, given the peculiarity of this type of cancer of having a very dense extra-tumoural matrix, which makes it difficult for drugs to reach conventional treatments.
“Magnetic hyperthermia is of special interest in this type of tumour because it can have a dual effect, helping the extracellular matrix to become more permeable, and causing the death of tumour cells. The synergy of this treatment with conventional therapies could be of great relevance,” explains Laura Asín, a researcher at the Instituto de Nanociencia y Materiales de Aragón (INMA, CSIC-UNIZAR) and CIBER-BBN.
Different types of biological models were used during the experiments. Using 3D cell models based on collagen gels, where pancreatic cancer cells are hosted, the alternating magnetic field conditions were optimised to obtain the maximum possible cell death. Experiments were then performed on a mouse model of pancreatic cancer, which showed, preliminarily, that magnetic hyperthermia treatment is able to stimulate the production of molecules related to the activation of the immune response.
“The activation of the individual’s own defences treated with magnetic hyperthermia could be a great advantage as it would provide an extra anti-tumour response with which to combat tumour cells,” adds Valeria Grazú, a researcher at INMA and CIBER-BBN.
Unpredictable and heterogeneous distribution
In this treatment, the magnetic nanoparticles are injected directly into the tumour, to ensure their presence in greater quantities in that area, and to obtain a better response. In this sense, one of the most novel and relevant advances of this work is that the magnetic nanoparticles present an unpredictable and heterogeneous bio-distribution in animals.
In some mice, the presence of these nanoparticles was detected in organs such as the spleen and liver, while in other cases the levels were undetectable and remained mainly in the tumour. The difference in bio-distribution could be related to the effectiveness of the treatment, as the animals with the highest nanoparticle load in the tumour grew less.
About INMA
The Instituto de Nanociencia y Materiales de Aragón (INMA) is a research institute created in 2020 by an agreement between the Consejo Superior de Investigaciones Científicas (CSIC) and the University of Zaragoza (UNIZAR) as a Joint Institute dependent on both institutions, as a result of the merger of the Instituto de Ciencia de Materiales de Aragón, ICMA, (founded in 1985, the first research institute of the University of Zaragoza (UNIZAR) and the first Materials Science Institute of the Spanish National Research Council (CSIC)) and the Institute of Nanoscience of Aragon, INA, (founded in 2003 by UNIZAR, which houses a unique set of instruments for the characterisation and fabrication of materials at the molecular scale). With around 300 members, INMA is organised in 6 research areas, two of them dedicated to “enabling research” (synthesis, processing and scaling of functional materials, and unique experimental technologies) and four to “key research topics” (materials for energy and environment, materials for biomedicine, materials for information technologies and new phenomena at the nanoscale). INMA has extensive experience in the participation and management of national and international research projects (more than 30 ongoing EU projects) and works in close collaboration with industry through private contracts.
About CIBER-BBN
The CIBER (Consorcio Centro de Investigación Biomédica en Red, M.P.) depends on the Instituto de Salud Carlos III -Ministerio de Ciencia e Innovación- and is co-financed by the European Regional Development Fund (ERDF). The CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) is made up of 46 research groups, selected on the basis of their scientific excellence, working mainly within three scientific programmes: Bioengineering and Biomedical Imaging, Biomaterials and Tissue Engineering and Nanomedicine. Its research is oriented towards the development of prevention, diagnosis and monitoring systems as well as technologies related to specific therapies such as Regenerative Medicine and Nanotherapies.
Pie de foto
Imagen 1: Lucía Gutiérrez, Jesús Martínez de la Fuente, Laura Asín, Raluca Fratila, Lilliane Beola y Yilian Fernández-Afonso.
Imagen 2: A) Imagen de microscopía electrónica de transmisión que muestra las nanopartículas magnéticas dentro de una célula tumoral. B) Imagen de anatomía patológica donde se ve la biodistribución de las nanopartículas magnéticas (de color marrón) en el tumor.
Publicación científica: “Critical parameters to improve pancreatic cancer treatment using magnetic hperthermia: Field conditions, immune response and particle biodistribution”. ACS Appl. Mater. Interfaces 2021, 13, 12982−12996 DOI: 10.1021/acsami.1c02338.
24/05/2021