Nanovesicles to induce fast and selective apoptotic death of neutrophils

ALTUBE MARÍA JULIA; SABIONE MARIA FLORENCIA; PEREZ ANA PAULA ; TREVANI ANALÍA; ROMERO EDER LILIA

Conferencia; 1st Zooming into preclinical nanomedicines in the era Covid19; 2020

Asociación Argentina de Nanomedicinas

Despite of playing a key role in immune surveillance, activated neutrophils may also cause part of the damages observed in some severe lung infections, chronic inflammation, or autoimmune diseases. Because of that, counting on agents different to classical corticosteroids to induce a rapid and selectively site-specific apoptotic death of recruited neutrophils, may constitute a smart therapeutic strategy to counterbalance tissue damages. In such scenario, we show here for thefirst time, that upon endocytic uptake by neutrophils nanoparticles made of archaeolipids [nanoarchaeosomes (nArc)] cause a pronouncedly different effect than the induced by nanoliposomes (nLip) made of ordinary lipids extracted from plants or animals. Here, two types of nanovesicles were incubated with human blood neutrophils:1) nLip made of HSPC and cholesterol (150 nm sized, ∼-3 mV ξ potential) and 2) nArc (150 nm sized, ∼ -40 mV ξ potential). The intracellular uptake of RhodaminePE labelled nanovesicles was assessed by flow cytometry and confocal microscopy, together with cell viability measured by annexin V and propidium iodidelabeling. It was found that upon 3 h, nArc was not only more extensively taken up by neutrophils than nLip, but also induced apoptosis in a dose dependent manner (at 70, 110, 225 and 450 µg/mL of lipids,7, 30, 60 and 70 % of neutrophil population were at early apoptosis, respectively). nLipon the other hand, caused no deleterious effects on neutrophiles. We conclude that nArc may constitute a nanotechnological platform that deserves a deeper exploration deeper exploration as inducer of neutrophil apoptosis in a pathological context.