A Synthetic Protocell-Based Heparin Scavenger

Qing Liu, Shuo Yang, Iris Seitz, Anna Maria Makri Pistikou, Tom F.A. de Greef*, Mauri A. Kostiainen*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)
24 Downloads (Pure)

Abstract

Heparin is a commonly applied blood anticoagulant agent in clinical use. After treatment, excess heparin needs to be removed to circumvent side effects and recover the blood-clotting cascade. Most existing heparin antidotes rely on direct heparin binding and complexation, yet selective compartmentalization and sequestration of heparin would be beneficial for safety and efficiency. However, such systems have remained elusive. Herein, a semipermeable protein-based microcompartment (proteinosome) is loaded with a highly positively charged chitosan derivative, which can induce electrostatics-driven internalization of anionic guest molecules inside the compartment. Chitosan-loaded proteinosomes are subsequently employed to capture heparin, and an excellent heparin-scavenging performance is demonstrated under physiologically relevant conditions. Both the highly positive scavenger and the polyelectrolyte complex are confined and shielded by the protein compartment in a time-dependent manner. Moreover, selective heparin-scavenging behavior over serum albumin is realized through adjusting the localized scavenger or surrounding salt concentrations at application-relevant circumstances. In vitro studies reveal that the cytotoxicity of the cationic scavenger and the produced polyelectrolyte complex is reduced by protocell shielding. Therefore, the proteinosome-based systems may present a novel polyelectrolyte-scavenging method for biomedical applications.

Original languageEnglish
Article number2201790
Number of pages6
JournalSmall
Volume19
Issue number13
Early online date15 May 2022
DOIs
Publication statusPublished - 29 Mar 2023
MoE publication typeA1 Journal article-refereed

Keywords

  • chitosan
  • electrostatic interactions
  • heparin
  • microcompartments
  • proteinosomes
  • selectivity
  • semipermeable

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