Nanosubmarine with self-destroying activity
Autonomous targeting and release of drugs at their site of action are desired features of nanomedical systems. Now, a team
of Dutch scientists has designed a nanomotor that has these functions: An antitumor drug encapsulated in self-propelled,
self-assembled stomatocytes is carried across the cellular membrane and released inside the cell upon a chemical redox signal
that disassembles the vesicle membrane. This deliver and unpack nanomedicinal system is introduced in the journal
Angewandte Chemie.
Self-propelling nanovesicles are attractive transport vehicles for drugs. If they are fueled by hydrogen peroxide, these
vesicles can take up directed motion responding to its concentration gradient. Combining the ideas of self-propelling
nanomotors, drug encapsulation, and triggered destruction of the nanocarrier, Daniela A. Wilson and her team at Radboud
University, The Netherlands, have designed an artificial self-propelling vesicle, which is sealed by a block copolymer shell
and opens to release the loaded drug load if it encounters higher concentrations of glutathione, a chemical signal inside
cells.
Glutathione is a so-called redox molecule, an antioxidant. In the cell, this small peptide acts as a scavenger of reactive
oxygen species; besides, it serves as a pool for the amino acid cysteine. Elevated levels of glutathione are frequently found
inside tumor cells. Wilson and her team came upon glutathione in their attempt to find a door-opener for their drug-loaded,
self-propelling artificial vesicles: “The small glutathione can enter into the PEG shell of the nanomotor and then break down
the redox-responsive disulfide bonds […], resulting in cleavage of the outside PEG shell,” they wrote. Thus, upon cleaving
disulfide bonds, glutathione triggers the vesicle membrane disassembly, and the content of the vesicle, which can be a drug,
is distributed in the target cell.
The material of the vesicle membrane is a block copolymer made of poly(ethylene glycol) (PEG) and polystyrene, both of
which are connected by a disulfide bond. During self-assembly, a hydrophilic anticancer drug can be encapsulated. Then, the
artificial vesicle is transformed into a bowl-shaped stomatocyte, a vesicle with a special dent or groove, by adding the
engine, platinum nanoparticles. This nanoparticle catalyst degrades hydrogen peroxide, which is typically produced by tumor
cells, propelling the stomatocytes forward, for example, across the cell membrane. There, glutathione, as it were, presses
the door handle, opens the vesicle, and stops the motion by catalyst poisoning.
For human cell cultures, the authors demonstrated internalization of the stomatocyte nanomotors, their degradation, and
drug release. They propose the nano-submarine as an attractive concept for future drug delivery applications
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About the Author
Dr. Daniela A. Wilson is Head of the Systems Chemistry Department at the Institute for Molecules and Materials, Radboud
University, Nijmegen, The Netherlands, and full professor at Radboud Institute for Molecular Life Sciences. The Wilson group
investigates smart functional materials and their application in non-equilibrium systems to create dynamic, responsive, and
adaptive nanosystems.
http://www.ru.nl/bio-orgchem/people/content/dr-daniela-wilson/