A Potential 3‐in‐1 Combined AntiSARS‐CoV‐2 Therapy Using Pulmonary MIL‐100(Fe) Formulation

The emergence and rapid propagation of infectious diseases, including the COVID-19 pandemic, has evidenced the vulnerabilities in global health surveillance, the ease of transmission, and the imperative need for effective treatments. In this context, nanomedicines based on metal-organic frameworks (MOFs) have garnered great relevance as promising drug delivery platforms in a large range of complex diseases (e.g., cancer, and infections). However, most research has focused on sensing with scarce examples in antiviral therapies. Hence, here a pioneer combined 3-in-1 effect anti-COVID pulmonary multitherapy based on the mesoporous iron(III) carboxylate MIL-100(Fe) nanoparticles is proposed, with the proven intrinsic MOF effect, associated with favipiravir drug into their porosity and heparin on their external surface. A significant antiviral effect against a real scenario of COVID-19 infection is demonstrated (≈70% inhibition), ensuring a suitable cellular viability. Further, a convenient pulmonary formulation is prepared based on mannitol-based microspheres, testing its safety and biodistribution in healthy mice. No significant side effects are observed, reaching successfully the deep lungs, emphasizing a reduced immunological response compared to their controls. Therefore, these promising results open new horizons for future (pre)clinical trials targeting challenging infectious/pulmonary pathologies, enhancing the feasibility of designing customized therapeutic MOF platforms.