Fluorous Phase‐Directed Peptide Assembly Affords Nano‐Peptisomes Capable of Ultrasound‐Triggered Cellular Delivery

Here, we report the design, synthesis and efficacy of a new class of ultrasound (US)‐sensitive self‐assembled peptide‐based nanoparticle. Peptisomes are prepared via templated assembly of a de novo designed peptide at the interface of fluorinated nanodroplets. Utilizing peptide assembly allows for facile particle synthesis, direct incorporation of bioactive sequences displayed from the particle corona, and the ability to easily encapsulate biologics during particle preparation using a mild solvent exchange procedure. Further, nano‐peptisome size can be precisely controlled by simply modulating the starting peptide and fluorinated solvent concentrations during synthesis. Biomolecular cargo encapsulated within the particle core can be directly delivered to the cytoplasm of cells upon US‐mediated rupture of the carrier. Thus, nano‐peptisomes represent a novel class of US‐activated carriers that can shuttle cell‐impermeable biomacromolecules into cells with spatial and temporal precision.     

Localized Supramolecular Peptide Self‐Assembly Directed by Enzyme‐Induced Proton Gradients

Electrodes are ideal substrates for surface localized self‐assembly processes. Spatiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode. The so‐used gradients of ions proved their effectiveness over the last decade but are in essence limited to material‐based electrodes, considerably reducing the scope of applications. Herein is described a strategy to enzymatically generate proton gradients from non‐conductive surfaces. In the presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film provides a flow of protons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid–liquid interface allows the self‐assembly of Fmoc‐AA‐OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides into β‐sheet nanofibers exclusively from and near the surface. In the absence of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc‐AA‐OH self‐assembly.