Publication on Science Translational Medicine

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A new study, carried out by the group of Daniele Catalucci from the CNR-IRGB (Milan, Italy), one of the key partners of the EU-funded project CUPIDO, demonstrated that nanoparticle-encapsulated pharmacologically active peptides can be efficiently delivered to the heart via inhalation. These results, published in the journal “Science Translational Medicine”, represent the first proof-of-concept for an unconventional and pioneering approach exploiting inhalable nanoparticle properties to improve diseased cardiac conditions.

As Michele Miragoli, first author of the paper explains: “Nanomedicine, meaning the application of nanotechnology to the health sector, represents a promising approach for near future health care. Indeed, several nanopharmaceuticals have been approved by the FDA since the late 90s’  leading to remarkable advantages especially in the cancer field. Curiously, only very few attempts have been made to apply nanomedicine to cardiovascular disease area in spite it represents the leading cause of death worldwide.

Among the treatments for cardiovascular disease, there is an increasing interest in peptide-based therapy due to their high selectivity. However, in many cases low half-life due to degradation and mandatory intra-venous injections are limiting their use and efficacy. Additionally, this type of administration is often associated with patient discomfort and low-compliance, making it problematic for chronic treatment.

The idea for an unconventional administration route to target the heart came from recent discoveries about atmospheric pollution: “It is now well-known that combustion-derived nanoparticles in the atmosphere can reach the heart. If toxic nanoparticles can translocate from the lungs to the heart, why do not exploit the same route to deliver therapeutic ones instead?” explains Daniele Catalucci, the corresponding author and project coordinator of CUPIDO.

 The innovative approach federating CUPIDO project and supported by the EU-funding, is based on previous works from the same team, showing that small biocompatible and biodegradable calcium phosphate nanoparticles can be incorporated by the cardiac cells and can release locally the carried drugs.

In this new study, the team makes a significant step beyond by demonstrating the high capacity of these nanoparticles to readily translocate from the pulmonary tree to the heart where the peptide cargo is finally released. Consequently, the diseased animal models treated by inhalation with the nanoparticle-encapsulated peptide displayed an improved myocardial contraction and restored cardiac function.

 The authors acknowledge that the mechanisms driving nanoparticles interactions with pulmonary barrier are still unknown and need further investigations, especially on the local tolerance of this new delivery approach.

These encouraging results open new avenues to optimize nanomaterials, combined with peptides, for inhalation as a more efficient and patient-friendly way to address cardiovascular diseases.