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Influence of Core Cross-Linking and Shell Composition of Polymeric Micelles on Immune Response and Their Interaction with Human Monocytes.
Gardey, Elena; Sobotta, Fabian H; Hoeppener, Stephanie; Bruns, Tony; Stallmach, Andreas; Brendel, Johannes C.
Affiliation
  • Gardey E; Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany.
  • Sobotta FH; Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Jena, Germany.
  • Hoeppener S; Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Jena, Germany.
  • Bruns T; Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Jena, Germany.
  • Stallmach A; Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Jena, Germany.
  • Brendel JC; Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Jena, Germany.
Biomacromolecules ; 21(4): 1393-1406, 2020 04 13.
Article in En | MEDLINE | ID: mdl-32084317
Block copolymer micelles have received increasing attention in the last decades, in particular for their appealing properties in nanomedicine. However, systematic investigations of the interaction between polymeric micelles and immune cells are still rare. Therefore, broader studies comparing the structural effects remain inevitable for a comprehensive understanding of the immune response and for the design of efficient, nonimmunogenic delivery systems. Here, we present novel block copolymer micelles with the same hydrophobic core, based on a copolymer of BA and VDM, and various hydrophilic shells ranging from common PEG derivatives to morpholine-based materials. The influence of these shells on innate immune responses was studied in detail. In addition, we investigated the impact of micelle stability by varying the cross-linking density in the micellar core. Surprisingly, whereas different shells had only a minor impact on immune response, micelles with reduced cross-linking density considerably enhanced the release of cytokines from isolated human monocytes. Moreover, the uptake of non-cross-linked micelles by monocytes was significantly higher as compared to cross-linked materials. Our study emphasizes the importance of the micellar stability on the interaction with the immune system, which is the key for any stealth properties in vivo. Polymers based on morpholines result in a similar low response as the PEG derivative and may represent an interesting alternative to the common PEGylation.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Monocytes / Micelles Limits: Humans Language: En Journal: Biomacromolecules Journal subject: BIOLOGIA MOLECULAR Year: 2020 Document type: Article Affiliation country: Germany Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Monocytes / Micelles Limits: Humans Language: En Journal: Biomacromolecules Journal subject: BIOLOGIA MOLECULAR Year: 2020 Document type: Article Affiliation country: Germany Country of publication: United States