Interactions of core cross-linked poly(2-oxazoline) and poly(2-oxazine) micelles with immune cells in human blood

Meike N Leiske; May Lai; Thakshila Amarasena; Thomas P Davis; Kristofer J Thurecht; Stephen J Kent; Kristian Kempe

doi:10.1016/j.biomaterials.2021.120843

Interactions of core cross-linked poly(2-oxazoline) and poly(2-oxazine) micelles with immune cells in human blood

Biomaterials. 2021 Jul:274:120843. doi: 10.1016/j.biomaterials.2021.120843. Epub 2021 May 4.

Authors

Meike N Leiske¹, May Lai¹, Thakshila Amarasena², Thomas P Davis³, Kristofer J Thurecht⁴, Stephen J Kent⁵, Kristian Kempe⁶

Affiliations

¹ ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
² ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, The University of Melbourne, Melbourne, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, 3000, Australia.
³ ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia; Centre for Advanced Imaging (CAI) and Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent Bio-Nano Science & Technology and ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St. Lucia, QLD, 4072, Australia.
⁴ Centre for Advanced Imaging (CAI) and Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent Bio-Nano Science & Technology and ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St. Lucia, QLD, 4072, Australia.
⁵ ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, The University of Melbourne, Melbourne, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, 3000, Australia; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC, 3800, Australia.
⁶ ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia; Materials Science and Engineering, Monash University, Clayton, VIC, 3800, Australia. Electronic address: kristian.kempe@monash.edu.

PMID: 33984635
DOI: 10.1016/j.biomaterials.2021.120843

Abstract

Water-soluble poly(cyclic imino ether)s (PCIEs) have emerged as promising biocompatible polymers for nanomedicine applications in recent years. Despite their generally accepted stealth properties, there has been no comprehensive evaluation of their interactions with primary immune cells in human blood. Here we present a library of core cross-linked micelles (CCMs) containing various PCIE shells. Well-defined high molar mass CCMs (M_n > 175 kDa, Ð < 1.2) of similar diameter (~20 nm) were synthesised using a cationic ring-opening polymerisation (CROP) - surfactant-free reversible addition-fragmentation chain-transfer (RAFT) emulsion polymerisation strategy. The stealth properties of the different PCIE CCMs were assessed employing a whole human blood assay simulating the complex blood environment. Cell association studies revealed lower associations of poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx) CCMs with blood immune cells compared to the respective poly(2-oxazine) (POz) CCMs. Noteworthy, PMeOx CCMs outperformed all other reported CCMs, showing overall low associations and only negligible differences in the presence and absence of serum proteins. This study highlights the importance of investigating individual nanomaterials under physiologically relevant conditions and further strengthens the position of PMeOx as a highly promising stealth material for biomedical applications.

Keywords: Core cross-linked micelle; Cyclic imino ether; Emulsion polymerisation; Immune cell interaction; RAFT polymerisation; Stealth effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Micelles*
Oxazines
Oxazoles
Polymerization
Polymers*

Substances

Micelles
Oxazines
Oxazoles
Polymers
poly(2-oxazoline)