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Synthetic nanoparticles as an innovative treatment for sepsis (SPRINT-4-SEPSIS)

19th national competition for scientific and technical research

Sepsis: Early Warning, Prevention and Treatment

Senior Researcher : Antonio Artigas Raventós

Research Centre or Institution : Instituto de Investigación e Innovación Parc Taulí (I3PT), Corporación Sanitaria i Universitaria Parc Taulí

Abstract

It is well established that mesenchymal stromal cells (MSC) through their paracrine activity, which is mediated, in part, by exosomes has a remarkable therapeutic effectiveness in regeneration and modulating the immune response.  

 We aim at developing a cell-free therapy based on the production of synthetic nanocapsules (NCs) encapsulating active components identified from MSC-derived exosomes cargo that will down-regulate inflammation, will assist the restoration of systemic immune homeostasis and improve the lung injury in a sepsis model.

During the second year of the project we have analized the protein and miRNA expresion profile of exosomes from non-activated and activated MSCs. Importantly, this analysis has revealed that pre-conditioning MSCs to a septic environment modifies the cargo of its exosomes, resulting in the appearance of proteins related to cell cycle regulation, cell proliferation and miRNAs with a key role on suppressing inflammation and enhancing immunoregulatory pathways.

Concerning the nanocarrier to deliver pre-selected exosomal components, we have developed new red fluorescent PLGA NCs with different surface charges. The performed in vitro studies showed that they are well preserved after cryo-storage for at least one month, are colloidally stable in tested culture and biological media and did not exhibit cytotoxic effects, even at very high concentrations, on two representative cell types in the pulmonary environment. In addition, we studied the NCs intracellular uptake confirming that the NCs are internalized by the 90% of the cells 4h after the treatment. In vivo studies demonstrated that our new carrier can be safely administered intratracheally, by inhalation and intravenously. Particularly, NCs are especially suitable as a pulmonary drug delivery system due to their satisfactory retention in lung tissue.

We believe that those first steps are very promising towards a cell-free therapeutic strategy for sepsis, identifying specific proteins and miRNAs that could be responsible for the exosomes therapeutic effect and by developing and characterizing a nanocarrier, that in the future, will make it an innovative and cell-free treatment for sepsis and lung injury related diseases. 

 

Scientific Production
 
Magazine Articles 2
Communications at national conferences 4
Communications at international conferences 3

 

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