TY - JOUR
T1 - Opsonin-Deficient Nucleoproteic Corona Endows UnPEGylated Liposomes with Stealth Properties in Vivo
AU - Giulimondi, Francesca
AU - Vulpis, Elisabetta
AU - Digiacomo, Luca
AU - Giuli, Maria Valeria
AU - Mancusi, Angelica
AU - Capriotti, Anna Laura
AU - Laganà, Aldo
AU - Cerrato, Andrea
AU - Zenezini Chiozzi, Riccardo
AU - Nicoletti, Carmine
AU - Amenitsch, Heinz
AU - Cardarelli, Francesco
AU - Masuelli, Laura
AU - Bei, Roberto
AU - Screpanti, Isabella
AU - Pozzi, Daniela
AU - Zingoni, Alessandra
AU - Checquolo, Saula
AU - Caracciolo, Giulio
N1 - Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.
PY - 2022/2/22
Y1 - 2022/2/22
N2 - 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.
AB - 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.
KW - gene delivery systems
KW - immune cell interactions
KW - lipoplexes
KW - liposomes
KW - protein corona
KW - stealth nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85123925991&partnerID=8YFLogxK
U2 - 10.1021/acsnano.1c07687
DO - 10.1021/acsnano.1c07687
M3 - Article
AN - SCOPUS:85123925991
SN - 1936-0851
VL - 16
SP - 2088
EP - 2100
JO - ACS Nano
JF - ACS Nano
IS - 2
ER -