Femtosecond Laser-Ablative Aqueous Synthesis of Multi-Drug Antiviral Nanoparticles

Nanomedicine offers a number of innovative strategies to address major public health burdens, including influenza and SARS-CoV-2. In this work, we introduce a multi-drug nanoparticle fabricated using femtosecond laser ablation which can be used for the treatment of influenza, SARS-CoV-2, and their co-infections. The influenza antiviral, baloxavir marboxil; the SARS-CoV-2 antiviral, remdesivir; and the anti-inflammatory drug, dexamethasone, were co-ablated in aqueous media, followed by surface modification with a cationic polymer to generate a nanoparticle with a diameter of ~73 nm and a positive zeta potential. We demonstrate high efficacy of these nanoparticles against Influenza Virus A using a clinically relevant, in vitro primary mouse trachea epithelial cell-air-liquid interface culture model. These findings demonstrate great promise both for the use of femtosecond laser ablation to generate multi-drug nanoparticles, as well as for the potential anti-viral effects of our nanoformulation against other respiratory virus infections such as SARS-CoV-2.