Opsonin-Deficient Nucleoproteic Corona Endows UnPEGylated Liposomes with Stealth Properties In Vivo

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.

The protein corona reduces the anticancer effect of graphene oxide in HER-2-positive cancer cells

“…to avoid the involving of opsonin proteins in the corona, guaranteeing the maintenance of the targeting efficiency of nanomedicines and the escape from the mononuclear phagocyte system [33]. Moreover, besides ligand and stealth polymer-based approach, recently the artificial protein corona has greatly emerged, namely by pre-coating the nanomaterials surface with antibodies or proteins to modulate the protein corona formation and induce an active cancer-targeting aimed at ensuring the specific therapeutic action of the system [34]. On the other hand, few studies have investigated how the altered interaction with the plasma membrane caused by the protein corona can influence the anticancer properties of nanomaterials.…”

“… 33 Moreover, besides ligand and stealth polymer-based approach, recently the artificial protein corona has greatly emerged, namely by pre-coating the nanomaterials surface with antibodies or proteins to modulate the protein corona formation and induce an active cancer-targeting aimed at ensuring the specific therapeutic action of the system. 34 On the other hand, few studies have investigated how the altered interaction with the plasma membrane caused by the protein corona can influence the anticancer properties of nanomaterials. In this study, we used SK-BR-3 human breast cancer cells as model system of HER-2 positive cancer cells and GO as a model of HER-2 inhibitor.…”

Tuning the immune system by nanoparticle–biomolecular corona

“…Negative surface charge/ Artificial BC Reduced immune system recognition due to limited interaction with plasma membrane 60 Size increase/aggregation Immune clearance 42,60 Opsonins enrichment Phagocytosis 61,62 Protein conformational changes Inflammatory response triggering 63 , amyloid fibrils formation, autoimmunity 64,65 66 . More recently, the negative charge of DNA was exploited to produce a multilayered biomimetic NP type called "proteoDNAsome" whose negatively charged BC allows to elude the immune system more efficiently than PEGylated liposomes in vivo 67 .…”

Versatile Protein Coronation Approach with Multiple Depleted Serum for Creating Biocompatible, Precision Nanomedicine

“…[ 13–14 ] To a similar end, a recent study revealed that the encasement with DNA species is helpful in attracting dysopsonin over opsonin. [ 15 ]…”

“…[13][14] To a similar end, a recent study revealed that the encasement with DNA species is helpful in attracting dysopsonin over opsonin. [15] A next-level precision nanomedicine is expected to be one carrying dedicated protein corona that functionally fulfils goals beyond long circulation. Technically, coating with protein corona frequently evolved a one-time incubation of nanomaterials with specific fluid (plasma or serum).…”