Dual Thermal- and Oxidation-Responsive Polymers Synthesized by a Sequential ROP-to-RAFT Procedure Inherently Temper Neuroinflammation


TURHAN DİDİKOĞLU Z. Y., d’Arcy R., El Mohtadi F., Teixeira L. I., Francini N., Geven M., ...More

Biomacromolecules, vol.24, no.10, pp.4478-4493, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 10
  • Publication Date: 2023
  • Doi Number: 10.1021/acs.biomac.2c01365
  • Journal Name: Biomacromolecules
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, MEDLINE
  • Page Numbers: pp.4478-4493
  • Akdeniz University Affiliated: Yes

Abstract

This study is about multiple responsiveness in biomedical materials. This typically implies “orthogonality” (i.e., one response does not affect the other) or synergy (i.e., one increases efficacy or selectivity of the other), but an antagonist effect between responses may also occur. Here, we describe a family of very well-defined amphiphilic and micelle-forming block copolymers, which show both oxidative and temperature responses. They are produced via successive anionic ring-opening polymerization of episulfides and RAFT polymerization of dialkylacrylamides and differ only in the ratio between inert (N,N-dimethylacrylamide, DMA) and temperature-sensitive (N,N-diethylacrylamide, DEA) units. By scavenging Reactive Oxygen Species (ROS), these polymers are anti-inflammatory; through temperature responsiveness, they can macroscopically aggregate, which may allow them to form depots upon injection. The localization of the anti-inflammatory action is an example of synergy. An extensive evaluation of toxicity and anti-inflammatory effects on in vitro models, including BV2 microglia, C8D30 astrocytes and primary neurons, shows a link between capacity of aggregation and detrimental effects on viability which, albeit mild, can hinder the anti-inflammatory potential (antagonist action). Although limited in breadth (e.g., only in vitro models and only DEA as a temperature-responsive unit), this study suggests that single-responsive controls should be used to allow for a precise assessment of the (synergic or antagonist) potential of double-responsive systems.