4.8 Article

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

期刊

BIOMATERIALS
卷 274, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120843

关键词

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

资金

  1. Australian Research Council [FT190100572]
  2. Alexander von Humboldt Foundation
  3. NHMRC [APP1148582, APP1136322]
  4. Australian Research Council Centre of Excellence in Convergent Bio-Nano Science Technology [CE140100036]
  5. Australian Research Council [FT190100572] Funding Source: Australian Research Council

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The study demonstrates that PMeOx polymer structures show weaker interactions with immune cells in human blood, indicating their potential advantages in biomedical applications.
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, D < 1.2) of similar diameter (similar to 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.

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