HE ERC Consolidator Grant 2023-2028

MAGNETIC HYPERTHERMIA FOR METASTASIZED TUMOR TREATMENT AND REMOTE MANIPULATION OF MICRODEVICES

Abstract: In magnetic hyperthermia (MHT), magnetic nanoparticles (MNPs) convert magneto-energy into heat under a time-varying magnetic field. MHT with MNPs is used in catalysis to promote reactions in solution and in cancer therapy, to ‘burn’ primary tumors in clinic, e.g. Glioblastoma, upon deposition of nanoparticles at the tumor site. The power of MHT, being an externally triggered approach to produce heat, goes beyond these actual uses. In GIULIa project I will apply MHT in tasks not yet explored to target the unmet needs of treatment of metastasized tumors and address MHT-mediated locomotion. MHT treatment of cancer metastases is now not doable because of scarce MNP dose accumulation at the spreading tumor sites. In GIULIa, MNPs designed for MHT, will be loaded in/on natural killer (NK) immune cells, which, intravenously injected, will deliver as Trojan horses the right dose of magnetic materials needed for MHT to the metastases. I will aim at raising the capability of NK and CAR-NK immune cells to infiltrate and recognize the tumor. This will merge synergic toxic effects of NK cells immunotherapy with MHT-heat damage of MNPs. Next, magnetic microdevices and their remote locomotion based on MHT-heat gradient, represent a new technological solution for delivery purposes with no tissue-depth attenuation for their actuation. Under MHT, I will explore the localization of heat spots on metallic magnetic-based heterostructures as a means to generate bubbles in a liquid and drag an ad hoc designed magnetic-microdevices to which the heterostructures are anchored. For the scale-up synthesis of metallic-magnetic heterostructures needed for the microdevices, I will merge an in-flow approach to an MHT-route synthesis. The heat at the MNP surface will be used as an in situ energy source to promote the growth of the metallic domain on the MNP. Advanced NK cells and microdevice technology of GIULIa will impact the medical fields of MNP/drug delivery, immunotherapy and smart robotics.

Total budget: 2.993.750,00€

Total contribution: 2.993.750,00€

H2020 ERC - Proof of Concept Grant 2020-2021

HyperCube: Gram scale production of ferrite nanocubes and thermo-responsive polymer coated nanocubes for medical applications and further exploitation in other hyperthermia fields

Abstract: This project aims at the scale up production, characterization, future commercialization and clinical translation of magnetic iron oxides nanocubes of high magnetic and structural quality and the design and production of an in-flow set up for the further functionalization of the nanocubes with a thermo-responsive (TR) polymer shell. The nanocubes and TR-nanocubes are aimed to be used primarily as heat mediators in magnetic hyperthermia (MH) and as heatmediated drug agents for the delivery of chemotherapeutic drugs in a heat triggered-mediated chemotherapy for the treatment of tumors. Their use as contrast agents in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) stands as secondary applications and it will also be relevant in this project. Indeed, given the control over the materials, the scale up synthesis of nanocubes and the in-flow production of TR-nanocubes, we will deliver an unprecedented benchmark scaled product of nanocubes with optimal magneto-heat properties that shall ensure the transition of such materials towards the market and the clinics. In comparison to the standardly used and commercially available magnetic nanoparticles, the high magneto-heat performances at clinically safe magnetic radiofrequency, of such nanocubes will impact the treatment of tumor by MH, by multiple aspects: i) requiring less dose of magnetic materials to be injected intratumorally; ii) unique actuation of dual combination therapy of MH and local heattriggered drug release, which also will favor a more efficacious therapy at reduced dose of magnetic materials; iii) further degradation and clearance of the heat-mediator nanocubes thus enabling the further investigation of tumour progression by MRI, overcoming the current limitation of iron oxide nanoparticles now employed in MH for the treatment of Glioblastoma Multiforme. Instead, their magnetic response at frequency range of 20-40 kHz will make them appealing as contrast agents in MPI.

Total budget: 150.000,00€

Total contribution: 150.000,00€

H2020 ERC - Starting Grant 2016-2020

Colloidal Inorganic Nanostructures for Radiotherapy and Chemotherapy

Abstract: The goal of ICARO is to develop a nanocrystal (NC) platform to merge radio and chemotherapy into a single entity that acts more specific towards tumor cells. Our goal is to establish protocols for the preparation of radiolabelled-NCs that will be easily translated to the medical practice for radiotherapy. In particular, our objective is to develop heterostructures that will combine radio and chemotherapy, the latter of which is based on the use of magnetic nanoparticles that can trigger drug release under exposure to an alternating magnetic field (AMF). The radiotherapy will be based on the insertion of radionuclides on semiconductor nanocrystals. During this first part of the project, we have started to develop magnetic nanoparticles and heterostructures that have optimized heat performances under AMF. This is crucial in order to reduce the dose of magnetic material and to exploit the heat to efficiently activate the release of drug molecules that are associated to the particles.

Total budget: 1.033.609,88€

Total contribution: 1.033.609,88€