Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well‐defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox‐based approaches to cancer therapy.
Graphene oxide has been widely deployed in electrical
sensors for
monitoring physical, chemical, and biological processes. The presence
of abundant oxygen functional groups makes it an ideal substrate for
integrating biological functional units to assemblies. However, the
introduction of this type of defects on the surface of graphene has
a deleterious effect on its electrical properties. Therefore, adjusting
the surface chemistry of graphene oxide is of utmost relevance for
addressing the immobilization of biomolecules, while preserving its
electrochemical integrity. Herein, we describe the direct immobilization
of glucose oxidase onto graphene oxide-based electrodes prepared by
Langmuir–Blodgett assembly. Electrochemical reduction of graphene
oxide allowed to control its surface chemistry and, by this, regulate
the nature and density of binding sites for the enzyme and the overall
responsiveness of the Langmuir–Blodgett biofilm. X-ray photoelectron
spectroscopy, surface plasmon resonance, and electrochemical measurements
were used to characterize the compositional and functional features
of these biointerfaces. Covalent binding between amine groups on glucose
oxidase and epoxy and carbonyl groups on the surface of graphene oxide
was successfully used to build up stable and active enzymatic assemblies.
This approach constitutes a simple, quick, and efficient route to
locally address functional proteins at interfaces without the need
for additives or complex modifiers to direct the adsorption process.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.