Cracking the Immune Fingerprint of Metal-Organic Frameworks

Human body is continuously in a never-ending chess game against pathogens. When the immune system, our natural defense tool, is weakened, these organisms are able to escape, collapsing the body contingency plan, which results in a pathological state. To overcome this checkmate status, emerging nanomedicines have been successfully employed as one of the best booming tactic for the immune response, manipulating the body defense tools for a specific recognition/elimination of pathological cells via active ingredient delivery. However, the vast majority of these drug delivery systems (DDS) has been often considered exclusively as passive vehicles. Among them, nanoscaled metal-organic frameworks (nanoMOFs) have attracted a great attention due to their versatility, allowing to carry and deliver exceptional drug payloads and to modulate their biological bypass. Nonetheless, their intrinsic immunogenicity character has been never addressed. Considering the immense possibilities that nanoMOFs offer as treatment platform, our purpose is unveiling the MOF immunological fingerprint, including an in-deep evaluation of the cellular oxidation balance, the inflammation & recruitment of immune cells and the precise Th1/Th2 cytokine profile triggered. This performance will make more feasible the design of customized immune-active MOF nanoplatforms according to targeted diseases, becoming the next ace up of the immune system sleeveThis work was partially supported by the Labex NanoSaclay financial support for the MSc studies (ANR-11-IDEX-0003-02) together with the CNRS, IMDEA Energy and Xunta de Galicia (GRC-ED431C 2020/02) funding. T.H. and P. H. acknowledge the regional Madrid founding (Talento 2018 Modality 2, (2018-T2/IND-11407), the Multifunctional Metallodrugs in Diagnosis and Therapy Network (MICIU, RED2018-102471-T) and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement Nº 897678. P. H. acknowledges the Spanish Ramón y Cajal Programme (grant agreement no. 2014-16823)