A Biomimetic DNA-Based Membrane Gate for Protein-Controlled Transport of Cytotoxic Drugs.
Conor LanpherePatrick M ArnottSioned Fôn JonesKatarina KorlovaStefan HoworkaPublished in: Angewandte Chemie (Weinheim an der Bergstrasse, Germany) (2020)
Chemistry is ideally placed to replicate biomolecular structures with tuneable building materials. Of particular interest are molecular nanopores, which transport cargo across membranes, as in DNA sequencing. Advanced nanopores control transport in response to triggers, but this cannot be easily replicated with biogenic proteins. Here we use DNA nanotechnology to build a synthetic molecular gate that opens in response to a specific protein. The gate self-assembles from six DNA strands to form a bilayer-spanning pore, and a lid strand comprising a protein-binding DNA aptamer to block the channel entrance. Addition of the trigger protein, thrombin, selectively opens the gate and enables a 330-fold increase inw the transport rate of small-molecule cargo. The molecular gate incorporates in delivery vesicles to controllably release enclosed cytotoxic drugs and kill eukaryotic cells. The generically designed gate may be applied in biomedicine, biosensing or for building synthetic cells.
Keyphrases
- drug induced
- single molecule
- circulating tumor
- cell free
- small molecule
- protein protein
- induced apoptosis
- binding protein
- cell cycle arrest
- amino acid
- nucleic acid
- circulating tumor cells
- high resolution
- cell death
- gold nanoparticles
- cell proliferation
- endoplasmic reticulum stress
- sensitive detection
- signaling pathway
- label free
- magnetic nanoparticles