Influence of Core Cross-Linking and Shell Composition of Polymeric Micelles on Immune Response and Their Interaction with Human Monocytes

Abstract

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.

Glutathione Reductase-Sensitive Polymeric Micelles for Controlled Drug Delivery on Arthritic Diseases

“…Those results were comparable to other studies using amphiphilic polymers of PEG and other fatty acids or polymers. 47,48 The polymeric micelles did not influence cell morphology (SEM analysis). In addition, the hemocompatibility of the polymeric micelles was assessed using human blood, as it is a critical parameter before regulatory approval.…”

Selective uptake into inflamed human intestinal tissue and immune cell targeting by wormlike polymer micelles

“…The polymer micelles were formed from an amphiphilic block copolymer which consists of a hydrophobic butyl acrylate copolymer (PBA) and PEO as hydrophilic block. 10 mol% of pyridyldisulfide ethyl acrylate (PDSA) were further included in the hydrophobic block to enable a sufficient crosslinking of the micelles after their assembly, which was found to minimize potential pro-inflammatory effects of such nanostructures 27,37,38 . The copolymer of PBA and PDSA was synthesized by reversible addition−fragmentation chain-transfer (RAFT) polymerization to guarantee a narrow molar mass distribution of the polymer chains (see SI for experimental details and characterization; Supplementary Table 1, Fig.…”

“…The required nanoparticles of different shape were prepared by self-assembly of amphiphilic block copolymers into micelles and subsequent crosslinking. Such polymeric micelles have already demonstrated their potential in nanomedicine [26][27][28][29] . Advantages of these self-assembled materials lie in the access to very small structures (< 50 nm) while maintaining narrow size distributions and the uniform and dense packing of hydrophilic chains on the surface (e.g.…”

ROS‐Sensitive Polymer Micelles for Selective Degradation in Primary Human Monocytes from Patients with Active IBD

“…[ 19 ] The polymers themselves, nanoparticles, and their oxidized products have to be biocompatible [ 20 ] and demonstrate noninflammatory properties. [ 21 ] Recently we have reported a straightforward process to create novel ROS‐sensitive polymeric micelles comprising thioether moieties, which can be oxidized in the presence of H 2 O 2 resulting in a disintegration of the micelle. [ 22 ] These polymeric nanoparticles are directly prepared in aqueous solution by polymerization induced self‐assembly (PISA), which represents a straightforward way to prepare polymer micelles circumventing tedious assembly steps.…”