Redox- and pH-Responsive Polymersomes with Ferrocene Moieties Exhibiting Peroxidase-like, Chemoenzymatic Activity and H₂O₂-Responsive Release Behavior

Abstract

The development of compartments for the design of cascade reactions in a local space requires a selective spatiotemporal control. The combination of enzyme-loaded polymersomes with enzymelike units shows a great potential in further refining the diffusion barrier and the type of reactions in nanoreactors. Herein, pH-responsive and ferrocene-containing block copolymers were synthesized to realize pH-stable and multiresponsive polymersomes. Permeable membrane, peroxidase-like behavior induced by the redox-responsive ferrocene moieties and release properties were validated using cyclovoltammetry, dye TMB assay, and rupture of host–guest interactions with β-cyclodextrin, respectively. Due to the incorporation of different block copolymers, the membrane permeability of glucose oxidase-loaded polymersomes was changed by increasing extracellular glucose concentration and in TMB assay, allowing for the chemoenzymatic cascade reaction. This study presents a potent synthetic, multiresponsive nanoreactor platform with tunable (e.g., redox-responsive) membrane properties for potential application in therapeutics.

Crosslinked and Multi‐Responsive Polymeric Vesicles as a Platform to Study Enzyme‐Mediated Undocking Behavior: Toward Future Artificial Organelle Communication

“…This appearance of phase‐segregated membrane is also found for the pure FcPsomes. [ 37,49 ] Considering the similar surface morphology of co‐assembled N 3 ‐FcPsomes (Figure 2e) and FcPsomes [ 37 ] one may hypothesize the presence of hydrophilic multicompartmentalized FcPsomes particles by cryo‐TEM images. Final AF4‐LS study on FcPsomes [ 37 ] exhibits the presence of (aggregated) vesicular structures with rho factor of 1–1.2.…”

“…[ 37,49 ] Considering the similar surface morphology of co‐assembled N 3 ‐FcPsomes (Figure 2e) and FcPsomes [ 37 ] one may hypothesize the presence of hydrophilic multicompartmentalized FcPsomes particles by cryo‐TEM images. Final AF4‐LS study on FcPsomes [ 37 ] exhibits the presence of (aggregated) vesicular structures with rho factor of 1–1.2. Here, we postulate similar vesicular structures for all N 3 ‐FcPsomes in (cryo‐)TEM images, at which further AF4‐LS study is needed to finalize the overall structure of N 3 ‐FcPsomes.…”

“…To achieve this concept, two different amphiphilic ferrocenecontaining photo-cross-linkable and pH-responsive block copolymers being methoxy-terminated (MeO-FcBCP) or azideterminated (N 3 -FcBCP) (a) were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization (more details in Supporting Information). [37] S1, Supporting Information). Gel permeation chromatography (GPC) results outline the desired low dispersity values for involved BCP at which molar masses of FcBCP and N 3 -FcBCP are relatively high than that to BCP without incorporated Fc units (Table S1, Supporting Information).…”

“…In collaboration with the Gallei group we have recently reported well‐defined crosslinked, pH‐stable, and multi‐responsive polymersomes (FcPsomes) by the assembly of ferrocene‐containing and pH‐responsive block copolymers. [ 37 ] FcPsomes have a significant adaptive response and possible potential to various stimuli such as pH, H 2 O 2 , (enzyme‐converted) biomolecules such as glucose and electric potential. The presence of redox‐responsive ferrocene (Fc) units in the FcPsomes membrane allows for a specific uptake of β ‐cyclodextrin derivative ( β ‐CD) due to the formation of a stable host–guest inclusion complexation, while the release of β ‐CD can be triggered by the rupture of the host–guest interaction via chemically induced oxidation of Fc by H 2 O 2 .…”

In Situ Construction of Ferrocene-Containing Membrane-Bound Nanofibers for the Redox Control of Cancer Cell Death and Cancer Therapy

“…The generation of • OH adjacent to the plasma membranes was assumed to shorten the distance between where • OH is generated and lipid peroxidation occurs. Meanwhile, the transformation from neutral Fc to positive-charged Fc + under acidic and oxidative environments, as demonstrated by previous studies, , was intended to improve the interactions between peptide nanofibers and negative-charged membranes, which might contribute to increasing membrane permeability and inducing membrane destruction. To reveal the advantage of DiFc-K-pY in producing membrane-bound nanofibers and • OH, two control peptides of Fc-K-pY and DiFc-K-Y that lack one Fc moiety or an ALP-responsive phosphate group were also included (Figures A and S1).…”