Synthetic/ECM-inspired hybrid platform for hollow microcarriers with ROS-triggered nanoporation hallmarks

Abstract

Reactive oxygen species (ROS) are key pathological signals expressed in inflammatory diseases such as cancer, ischemic conditions and atherosclerosis. An ideal drug delivery system should not only be responsive to these signals but also should not elicit an unfavourable host response. This study presents an innovative platform for drug delivery where a natural/synthetic composite system composed of collagen type I and a synthesized polythioether, ensures a dual stimuli-responsive behaviour. Collagen type I is an extracellular matrix constituent protein, responsive to matrix metalloproteinases (MMP) cleavage per se. Polythioethers are stable synthetic polymers characterized by the presence of sulphur, which undergoes a ROS-responsive swelling switch. A polythioether was synthesised, functionalized and tested for cytotoxicity. Optimal conditions to fabricate a composite natural/synthetic hollow sphere construct were optimised by a template-based method. Collagen-polythioether hollow spheres were fabricated, revealing uniform size and ROS-triggered nanoporation features. Cellular metabolic activity of H9C2 cardiomyoblasts remained unaffected upon exposure to the spheres. Our natural/synthetic hollow microspheres exhibit the potential for use as a pathological stimuli-responsive reservoir system for applications in inflammatory diseases.

The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development

“…Finally, the polystyrene core is removed with tetrahydrofuran, leaving behind the hollow collagen sphere. To date, such scaffolds have been used for gene, growth factor, and drug delivery or ROS scavenging …”

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

“…The first case is shown by the oxidants themselves (auto‐accelerating behavior, see Figure A), but can also occur in enzymatic reactions. This is probably the case of hollow spheres of PPS and collagen, which show oxidant‐induced nanoporation and potentially also enzymatic degradation upon oxidation . In the second case (avidity), oxidation can remove the necessary proximity between positive charges (either disrupting hydrophobic association, or cleaving the polymer chain), thereby reversing the complexation of polycations with nucleic acids.…”

Reactive oxygen species‐responsive degradable poly(amino acid)s for biomedical use

“…10,11 For example, thioether possesses a specific sulfur (S) group that can be transformed into a hydrophilic S O group under oxidative conditions to generate ROS-switchable materials. [12][13][14] Methionine, a natural amino acid, is an ROS-responsive material that contains a thioether moiety and shows outstanding biocompatibility. [15][16][17][18] Amino acids are the basic structural units of proteins.…”