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

Francesca Giulimondi, Elisabetta Vulpis, Luca Digiacomo, Maria Valeria Giuli, Angelica Mancusi, Anna Laura Capriotti, Aldo Laganà, Andrea Cerrato, Riccardo Zenezini Chiozzi, Carmine Nicoletti, Heinz Amenitsch, Francesco Cardarelli, Laura Masuelli, Roberto Bei, Isabella Screpanti, Daniela Pozzi, Alessandra Zingoni, Saula Checquolo*, Giulio Caracciolo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2088-2100
Number of pages13
JournalACS Nano
Issue number2
Publication statusPublished - 22 Feb 2022


  • gene delivery systems
  • immune cell interactions
  • lipoplexes
  • liposomes
  • protein corona
  • stealth nanoparticles

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Fields of Expertise

  • Human- & Biotechnology


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