Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators

Monika Kluzek*, Yaara Oppenheimer-Shaanan, Tali Dadosh, Mattia I. Morandi, Ori Avinoam, Calanit Raanan, Moshe Goldsmith, Ronit Goldberg, Jacob Klein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities in the form of biofilms, present a strong challenge to therapeutic treatment due to resistance to conventional antimicrobial therapies. Liposomes can provide a versatile drug-vector strategy for biofilm treatment, but are limited by the need to balance colloidal stability with biofilm penetration. We have discovered a liposomic functionalization strategy, using membrane-embedded moieties of poly[2-(methacryloyloxy)ethyl phosphorylcholine], pMPC, that overcomes this limitation. Such pMPCylation results in liposomic stability equivalent to current functionalization strategies (mostly PEGylation, the present gold-standard), but with strikingly improved cellular uptake and cargo conveyance. Fluorimetry, cryo-electron, and fluorescence microscopies reveal a far-enhanced antibiotic delivery to model Pseudomonas aeruginosa biofilms by pMPC-liposomes, followed by faster cytosolic cargo release, resulting in significantly greater biofilm eradication than either PEGylation or free drug. Moreover, this combination of techniques uncovers the molecular mechanism underlying the enhanced interaction with bacteria, indicating it arises from bridging by divalent ions of the zwitterionic groups on the pMPC moieties to the negatively charged lipopolysaccharide chains emanating from the bacterial membranes. Our results point to pMPCylation as a transformative strategy for liposomal functionalization, leading to next-generation delivery systems for biofilm treatment.

Original languageAmerican English
Pages (from-to)15792-15804
Number of pages13
JournalACS Nano
Volume16
Issue number10
DOIs
StatePublished - 25 Oct 2022
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank for support: Israel Ministry of Science and Industry (grant 713272), Israel Science Foundation-National Science Foundation China joint program (grant ISF-NSFC 2577/17), European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 743016). This work was made possible in part by the historic generosity of the Harold Perlman family.

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

Keywords

  • antibiotic resistance
  • biofilm
  • drug delivery
  • liposome functionalization
  • zwitterionic polymer-bacteria membrane interactions

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