Nano-bio interface between human plasma and niosomes with different formulations indicates protein corona patterns for nanoparticle cell targeting and uptake

Unraveling the proteins interacting with nanoparticles (NPs) in biological fluids, such as blood, is pivotal to rationally design NPs for drug delivery. The protein corona (PrC), formed on the NP surface, represents an interface between biological components and NPs, dictating their pharmacokinetics and biodistribution. PrC composition depends on biological environments around NPs and on their intrinsic physicochemical properties. We generated different formulations of non-ionic surfactant/non-phospholipid vesicles, called niosomes (NIOs), using polysorbates which are biologically safe, cheap, non-toxic and scarcely immunogenic. PrC composition and relative protein abundance for all designed NIOs were evaluated ex vivo in human plasma (HP) by quantitative label-free proteomics. We studied the correlation of the relative protein abundance in the corona with cellular uptake of the PrC-NIOs in healthy and cancer human cell lines. Our results highlight the effects of polysorbates on nano-bio interactions to identify a protein pattern most properly aimed to drive the NIO targeting in vivo, and assess the best conditions of PrC-NIO NP uptake into the cells. This study dissected the biological identity in HP of polysorbate-NIOs, thus contributing to shorten their passage from preclinical to clinical studies and to lay the foundations for a personalized PrC.