Domingo F. Barber
Group Leader
Research summary
The overall objective of our group is to understand nanomedicine-mediated molecular and cellular mechanisms in new nanomedicine-based therapeutic applications developed for the treatment of cancer or autoimmunity, and to use this knowledge to bring these therapies closer to clinical application.
Publications
Mulens-Arias V, Rojas JM, Sanz-Ortega L, Portilla Y, Pérez-Yagüe S, Barber DF Polyethylenimine-coated superparamagnetic iron oxide nanoparticles impair in vitro and in vivo angiogenesis. Nanomedicine 2019;Oct;21:102063. doi: 10.1016/j.nano.2019.102063.
Sanz-Ortega L, Portilla Y, Pérez-Yagüe S, Barber DF. Magnetic targeting of adoptively transferred tumour-specific nanoparticle-loaded CD8+ T cells does not improve their tumour infiltration in a mouse model of cancer but promotes the retention of these cells in tumour-draining lymph nodes. J Nanobiotechnology. 2019 Aug 6;17(1):87. doi: 10.1186/s12951-019-0520-0.
Del Sol-Fernández S, Portilla-Tundidor Y, Gutiérrez L, Odio OF, Reguera E, Barber DF, Morales MP. Flower-like Mn-Doped Magnetic Nanoparticles Functionalized with αvβ3-Integrin-Ligand to Efficiently Induce Intracellular Heat after Alternating Magnetic Field Exposition, Triggering Glioma Cell Death. ACS Appl Mater Interfaces. 2019 Jul 31;11(30):26648-26663. doi: 10.1021/acsami.9b08318
Sanz-Ortega L, Rojas JM, Marcos A, Portilla Y, Stein JV, Barber DF T cells loaded with magnetic nanoparticles are retained in peripheral lymph nodes by the application of a magnetic field J Nanobiotechnology 2019 Jan 22;17(1):14. doi: 10.1186/s12951-019-0440-z.
Mejías R, Hernández Flores P, Talelli M, Tajada-Herráiz JL, Brollo MEF, Portilla Y, Morales MP, Barber DFCell-Promoted Nanoparticle Aggregation Decreases Nanoparticle-Induced Hyperthermia under an Alternating Magnetic Field Independently of Nanoparticle Coating, Core Size, and Subcellular Localization. ACS Appl Mater Interfaces 2019 Jan 9;11(1):340-355. doi: 10.1021/acsami.8b18451
Due to their small size and physicochemical properties, superparamagnetic iron oxide nanoparticles (SPION) have great potential as a nanomedicine in the fight against cancer, as they have proven effective for targeted drug release and in diagnosis by magnetic resonance imaging. SPIONs also show considerable promise for two additional cancer therapies, intracellular hyperthermia induction and targeting in cell transfer. Adoptive cell transfer is a type of immunotherapy that exploits the antitumour capacity of cytotoxic lymphocytes. The application of alternating magnetic fields (AMF) can magnetically induce intracellular hyperthermia in SPION-loaded cells, which can be used in cancer treatment. Results to date, using SPIONs in vitro studies and in animal models, suggest potential for rapid translation of these technologies to clinical practice. This development has nonetheless been delayed in part by a lack of basic knowledge of SPION-induced molecular and cellular mechanisms and the routes that regulate SPION degradation in the organism, both of which affect the therapeutic effectiveness of SPIONs and their accumulation and long-term toxicity.
The overall objective of our group is to understand SPION-mediated molecular and cellular mechanisms in distinct biomedical applications oriented to cancer and autoimmunity treatment, and to use this knowledge to improve SPION functional design for specific biomedical purposes in antitumour therapy. We pursue six specific objectives:
1. Investigate the ability of intracellularly loaded SPIONs to induce biological effects following the application of an AMF, to identify effects that depend on temperature increase or that are mediated by other mechanisms.
2. Comparative analysis of the effectiveness of various nanoparticle-targeting approaches in antitumour therapies.
3. Study SPION-induced immunogenic and epigenetic changes in cells and the possible contribution of AMF application in intracellular hyperthermia treatment on these changes.
4. Study of SPION degradation and transformation within lysosomes.
5. Potentiation of antitumour therapy by adoptive transfer of NK cells and CD8+ T cells using SPIONs.
6. Potentiation of autoimmunity treatment by adoptive transfer of immunosuppressive cells using SPIONs.
