Final Report Summary - BIOMAG (Magnetic Biomaterials: Magnetically Loaded Stem Cells as Diagnostic and Therapeutic Vectors for Lung Cancer)
Lung cancer is the biggest killer among all cancers. By the time clinical manifestation appears there is often lymph node spread and distant metastases, reducing the chances of an effective treatment. The improvement in survival expectancy of lung cancer patients depends, among others, in the ability to deliver therapeutic agents to the tumour and its metastases. Despite the introduction of new chemotherapies lung cancer survival is unchanged from thirty years ago, which makes specialists call for new approaches to treat this disease. Motivated by the previous facts, and relying upon a solid collaboration across several disciplines such as physics, medicine, chemistry and engineering, the present project aims for a substantially better way of treating lung cancer.
The restricted blood circulation in tumour cells makes them particularly susceptible to temperature changes. Accordingly, we hypothesise that modified mesenchymal stem cells (MSCs) may be used to deliver magnetic nanoparticles through their engraftment, killing both tumour epithelium and tumour vasculature, while preserving healthy tissue. This selective attack is possible due to the fact that magnetic nanoparticles can generate heat under the action of an alternating current (AC) magnetic field, a process called magnetic hyperthermia. Both the immuno-privileged character of MSCs and their preferential homing to tumour tissues allowing systemic delivery to widespread tumour and metastases, make them attractive as carriers. Therefore, introducing bio-compatible iron-oxide magnetic nanoparticles into the MSCs enables localised cellular-level sensing and heating while retaining the full viability and functionality of the MSCs.
One of the principal aims of this project was to obtain and characterise new magnetic nanoparticles with improved heat-evolving characteristics, to reach a fully tuneable magnetic heating system and the highest available contrast in magnetic resonance imaging (MRI), while preserving the viability of MSCs. Although other materials have been taken into consideration, we have concentrated our efforts in the magnetic phases of the iron oxides family (maghemite and magnetite), given the fact that they constituted the only system approved by the food & drug agency (FDA) for the time being to be used in humans. Our formulations tested so far have delivered very promising results, indicating that we are on the right path to match or even improve the compound set as a standard for applications based on magnetic hyperthermia, commercialised by Bayer-Shering Pharma under the generic name Resovist®. In order to ensure the targeting for cancer cells, surface engineering of the nanoparticles through bio-compatible coatings and specific antibodies has been also a central task in this work.
Another point of interest within the framework defined by the present project was that related to the improvement and development of imaging techniques suited for studying the uptaking and delivering processes of magnetic nanoparticles by MSCs, besides the routine characterisation of the nanoparticles. Taking into account the typical length scales involved in the materials of interest - nanometres range - transmission electron microscopy (TEM) has been our choice. In partnership with well known companies in both microscopy and bio-sensing industry, we have started the design of a ground-breaking imaging technique that will enable to uncover the foundations of magnetic hyperthermia at the nanoscale, while overcoming the barriers associated to the use of electrons for characterising biological specimens.
The restricted blood circulation in tumour cells makes them particularly susceptible to temperature changes. Accordingly, we hypothesise that modified mesenchymal stem cells (MSCs) may be used to deliver magnetic nanoparticles through their engraftment, killing both tumour epithelium and tumour vasculature, while preserving healthy tissue. This selective attack is possible due to the fact that magnetic nanoparticles can generate heat under the action of an alternating current (AC) magnetic field, a process called magnetic hyperthermia. Both the immuno-privileged character of MSCs and their preferential homing to tumour tissues allowing systemic delivery to widespread tumour and metastases, make them attractive as carriers. Therefore, introducing bio-compatible iron-oxide magnetic nanoparticles into the MSCs enables localised cellular-level sensing and heating while retaining the full viability and functionality of the MSCs.
One of the principal aims of this project was to obtain and characterise new magnetic nanoparticles with improved heat-evolving characteristics, to reach a fully tuneable magnetic heating system and the highest available contrast in magnetic resonance imaging (MRI), while preserving the viability of MSCs. Although other materials have been taken into consideration, we have concentrated our efforts in the magnetic phases of the iron oxides family (maghemite and magnetite), given the fact that they constituted the only system approved by the food & drug agency (FDA) for the time being to be used in humans. Our formulations tested so far have delivered very promising results, indicating that we are on the right path to match or even improve the compound set as a standard for applications based on magnetic hyperthermia, commercialised by Bayer-Shering Pharma under the generic name Resovist®. In order to ensure the targeting for cancer cells, surface engineering of the nanoparticles through bio-compatible coatings and specific antibodies has been also a central task in this work.
Another point of interest within the framework defined by the present project was that related to the improvement and development of imaging techniques suited for studying the uptaking and delivering processes of magnetic nanoparticles by MSCs, besides the routine characterisation of the nanoparticles. Taking into account the typical length scales involved in the materials of interest - nanometres range - transmission electron microscopy (TEM) has been our choice. In partnership with well known companies in both microscopy and bio-sensing industry, we have started the design of a ground-breaking imaging technique that will enable to uncover the foundations of magnetic hyperthermia at the nanoscale, while overcoming the barriers associated to the use of electrons for characterising biological specimens.