Block Length-Dependent Protein Fouling on Poly(2-oxazoline)-Based Polymersomes: Influence on Macrophage Association and Circulation Behavior.
atomistic simulations
nanoparticles
protein corona
protein fouling
zebrafish embryos
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
05
05
2022
received:
30
03
2022
pubmed:
8
6
2022
medline:
9
7
2022
entrez:
7
6
2022
Statut:
ppublish
Résumé
Polymersomes are vesicular structures self-assembled from amphiphilic block copolymers and are considered an alternative to liposomes for applications in drug delivery, immunotherapy, biosensing, and as nanoreactors and artificial organelles. However, the limited availability of systematic stability, protein fouling (protein corona formation), and blood circulation studies hampers their clinical translation. Poly(2-oxazoline)s (POx) are valuable antifouling hydrophilic polymers that can replace the current gold-standard, poly(ethylene glycol) (PEG), yet investigations of POx functionality on nanoparticles are relatively sparse. Herein, a systematic study is reported of the structural, dynamic and antifouling properties of polymersomes made of poly(2-methyl-2-oxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PMOXA-b-PDMS-b-PMOXA). The study relates in vitro antifouling performance of the polymersomes to atomistic molecular dynamics simulations of polymersome membrane hydration behavior. These observations support the experimentally demonstrated benefit of maximizing the length of PMOXA (degree of polymerization (DP) > 6) while keeping PDMS at a minimal length that still provides sufficient membrane stability (DP > 19). In vitro macrophage association and in vivo blood circulation evaluation of polymersomes in zebrafish embryos corroborate these findings. They further suggest that single copolymer presentation on polymersomes is outperformed by blends of varied copolymer lengths. This study helps to rationalize design rules for stable and low-fouling polymersomes for future medical applications.
Identifiants
pubmed: 35670200
doi: 10.1002/smll.202201993
doi:
Substances chimiques
Oxazoles
0
poly(2-oxazoline)
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2201993Subventions
Organisme : Swiss National Science Foundation
ID : P2BSP2_168751
Pays : Switzerland
Organisme : Medical Research Council
ID : MR/R015651/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 209121/Z/17/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C71717/A30035
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 209121_Z_17_Z
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Small published by Wiley-VCH GmbH.
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