Abstract
For several decades, surface grafted polyethylene glycol (PEG) has been a go-to strategy for preserving the synthetic identity of liposomes in physiological milieu and preventing clearance by immune cells. However, the limited clinical translation of PEGylated liposomes is mainly due to the protein corona formation and the subsequent modification of liposomes’ synthetic identity, which affects their interactions with immune cells and blood residency. Here we exploit the electric charge of DNA to generate unPEGylated liposome/DNA complexes that, upon exposure to human plasma, gets covered with an opsonin-deficient protein corona. The final product of the synthetic process is a biomimetic nanoparticle type covered by a proteonucleotidic corona, or “proteoDNAsome”, which maintains its synthetic identity in vivo and is able to slip past the immune system more efficiently than PEGylated liposomes. Accumulation of proteoDNAsomes in the spleen and the liver was lower than that of PEGylated systems. Our work highlights the importance of generating stable biomolecular coronas in the development of stealth unPEGylated particles, thus providing a connection between the biological behavior of particles in vivo and their synthetic identity.
Highlights
For several decades, surface grafted polyethylene glycol (PEG) has been a go-to strategy for preserving the synthetic identity of liposomes in physiological milieu and preventing clearance by immune cells
At least two main requisites must be implemented into an ideal nonviral, liposome-based gene-delivery systems (GDSs), which may appear as mutually exclusive: (i) capability to interact with biological membranes, favoring endosomal escape and cargo release within the target cells;[4] (ii) stealth properties to prevent, at the same time, clearance by circulating blood cells.[5]
We demonstrate the capacity of proteoDNAsomes to avoid capture by immune cells in vitro by using the human monocytic THP-1 and ex vivo leukocyte subpopulations derived from healthy donors
Summary
Surface grafted polyethylene glycol (PEG) has been a go-to strategy for preserving the synthetic identity of liposomes in physiological milieu and preventing clearance by immune cells. ACS Nano www.acsnano.org concerning requisite (ii), the positive charge of CLs elicits the adsorption of biomolecules from human blood, especially proteins, which in turn induce extensive aggregation and masking of the designed functionality.[2] In particular, it was demonstrated that the peculiar adsorption of opsonins on the CL surface (e.g., IgG complement proteins etc.) stimulates phagocytosis and rapid clearance of CLs from blood circulation. Of note, this effect is not completely prevented by CL-surface functionalization by poly(ethylene glycol) (PEG), as previously thought.[7]
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