Lipooligosaccharides As Amphiphiles to Build Liposomes for Effective Drug Delivery: the Case of Anticancer Ruthenium Complex‐Based Aggregates

Liposomes are complex aggregates, often including polyethylene glycol (PEG) to expand their life span in vivo, although their full biocompatibility is still questioned. With the aim to suitably replace PEG within liposomal formulations, here we propose a new liposomes formulation, which includes an amphiphilic molecule of natural origin: the lipooligosaccharide (LOS) from the Gram-negative bacterium Rhizobium rubi. LOS architecture is bifunctional: the lipid moiety at one terminus promotes its insertion into the liposome, the other terminus is hydrophilic and in this case presents an oligosaccharide motif similar to the human Lewis B antigen. Liposomes were prepared by co-formulating de-O-acylated LOS (de-LOS) with the lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and the anticancer nucleolipid-based Ru(III) complex, ToThyRu. In-depth microstructural characterization shows that de-LOS containing liposomes are stable aggregates. In vitro preliminary bioscreens have disclosed their negligible toxic profile and a good uptake in MCF-7 and HaCaT cells. The results validate the use of lipooligosaccharides in formulating liposomes and pave the way to their use in drug delivery applications.