Nebulized Hybrid Nanoarchaeosomes: Anti-Inflammatory Activity, Anti-Microbial Activity and Cytotoxicity on A549 Cells

SOFIA GIULIANA GUERIN STABILE; NOELIA PEREZ; HORACIO EMANUEL JEREZ; ESTEFANÍA BUTASSI; MARTIN DANIEL MIZRAHI; MATIAS LEONARDO NOBILE; ANA PAULA PEREZ ; MARIA JOSE MORILLA; LETICIA HERMINIA HIGA; EDER LILIA ROMERO

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2025

1422-0067

The properties of two hybrid nanoarchaeosomes (hybrid nanoARCs) made ofarchaeolipids extracted from the halophilic archaea Halorubrum tebenquichense and combiningthe properties of archaeolipid bilayers with metallic nanoparticles are exploredhere. BS-nanoARC, consisting of a nanoARC loaded with yerba mate (Ilex paraguariensis)extract (YME)-biogenic silver nanoparticles (BSs), and [BS + BS-nanoARC], consistent of aBS-nanoARC core covered by an outer shell of BSs, were structurally characterized andtheir therapeutic activities screened. By employing 109 ± 5 μg gallic acid equivalents(GAEs) and 73.4 μg chlorogenic acid/ YME mg as a silver reductive agent, spherical, heterogeneouslysized (~80 nm diameter), −27 mV ζ potential, 90% Ag0 and λmax 420 nmBSs were obtained. We further prepared ~100–200 nm diameter, −57 mV ζ potentialBS-nanoARC and ~300 nm diameter, −37 mV ζ potential [BS + BS-nanoARCs]. Freshlyprepared and nebulized BS-nanoARCs reduced the release of TNF-α, IL-6 and IL-8 by LPSirritatedTHP-1-macrophages and were highly anti-planktonic against S. aureus (MIC90:13 ± 0.8 μg Ag/mL). While the nanoARCs and BS-nanoARCs were innocuous, freshlyprepared [BS + BS-nanoARCs] magnified the cytotoxicity of BSs (IC50 12 μg Ag/mL vs.IC50 ~36 μg Ag/mL) on A549 cells. Such cytotoxicity remained after 30 days in the dark at4 ◦C, while that of BSs was lost. Freshly prepared BSs also lost activity upon nebulization,whereas freshly prepared [BS + BS-nanoARCs] did not. However, the cytotoxicity of the[BS + BS-nanoARCs] was also lost when nebulized after 30 days of storage. Despite theharmful effects of storage and mechanical stress on the structure of the more active [BS + BSnanoARCs],hybrid nanoARCs are promising examples of nanomedicines combining theproperties of archaeolipids with antimicrobial silver nanoparticles and anti-inflammatorypolyphenols that could complement oncologic therapies, reducing the usage of classicalantitumoral agents, corticosteroids, and, importantly, of antibiotics, as well as their waste.