6 Materialchemie
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- 2020 (2) (entfernen)
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- Englisch (2)
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- ja (2)
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- Amyloid (1)
- Graphene (1)
- NEXAFS (1)
- Nanoparticle (1)
- Nanostructure (1)
- Peptide (1)
- SAXS (1)
- Self-degrading (1)
- Small-angle X-ray scattering (1)
- Thumor therapy (1)
Organisationseinheit der BAM
The hexapeptide hIAPP22–27 (NFGAIL) is known as a crucial amyloid core sequence of the human islet amyloid polypeptide (hIAPP) whose aggregates can be used to better understand the wild‐type hIAPP′s toxicity to β‐cell death. In amyloid research, the role of hydrophobic and aromatic‐aromatic interactions as potential driving forces during the aggregation process is controversially discussed not only in case of NFGAIL, but also for amyloidogenic peptides in general. We have used halogenation of the aromatic residue as a strategy to modulate hydrophobic and aromatic‐aromatic interactions and prepared a library of NFGAIL variants containing fluorinated and iodinated phenylalanine analogues. We used thioflavin T staining, transmission electron microscopy (TEM) and small‐angle X‐ray scattering (SAXS) to study the impact of side‐chain halogenation on NFGAIL amyloid formation kinetics. Our data revealed a synergy between aggregation behavior and hydrophobicity of the phenylalanine residue. This study introduces systematic fluorination as a toolbox to further investigate the nature of the amyloid self‐assembly process.
Low biodegradability of graphene derivatives and related health risks are the main limiting factors for their in vivo biomedical applications. Here, we present the synthesis of enzyme-functionalized graphene sheets with self-degrading properties under physiological conditions and their applications in Tumor therapy. The synergistic enzyme cascade glucose oxidase and myeloperoxidase are covalently conjugated to the surface of graphene sheets and two-dimensional (2D) platforms are obtained that can produce sodium hypochlorite from glucose. The enzyme-functionalized graphene sheets with up to 289 nm average size are degraded into small pieces (≤40 nm) by incubation under physiological conditions for 24 h. Biodegradable graphene sheets are further loaded with doxorubicin and their ability for Tumor therapy is evaluated in vitro and in vivo. The laser-triggered release of doxorubicin in combination with the enzymatic activity of the functionalized graphene sheets results in a synergistic antitumor activity.
Taking advantage of their neutrophil-like activity, fast biodegradability, high photo- and chemotherapeutic effects, the novel two-dimensional nanoplatforms can be used for tumor therapeutic applications.