An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo.

The synthesis and characterization of an NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload "cargo" molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.

Quinone-Modified Mn-Doped ZnS Quantum Dots for Room-Temperature Phosphorescence Sensing of Human Cancer Cells That Overexpress NQO1.

Early detection of cancer cells in a rapid and sensitive approach is one of the great challenges in modern clinical cancer care. This study has demonstrated the first example of a rapid, selective, and sensitive phosphorescence probe based on phosphorescence energy transfer (PET) for cancer-associated human NAD(P)H: quinone oxidoreductase isozyme 1 (NQO1). An efficient room-temperature phosphorescence NQO1 probe was constructed by using Mn-doped ZnS quantum dots (Mn:ZnS QDs) as donors and trimethylquinone propionic acids as acceptors. Phosphorescence quenching of Mn:ZnS QDs from the Mn:ZnS QDs to a covalently bonded quinone was achieved through PET. Phosphorescence of Mn:ZnS QDs was turned on by the rapid reduction-initiated removal of the quinone quencher by NQO1. This probe shows low cellular toxicity and can rapidly distinguish between NQO1-expressing and -nonexpressing cancer cell lines through phosphorescence imaging.

Redox responsive Pd(ii) templated rotaxane nanovalve capped mesoporous silica nanoparticles: a folic acid mediated biocompatible cancer-targeted drug delivery system.

In this study, we report a redox responsive drug delivering nanocarrier design based on mesoporous silica nanoparticles. Gatekeeping of the mesopore is achieved using Pd(ii) templated, mechanically interlocked rotaxane nanovalves with a folic acid terminal group, anchored by a disulfide bridge as a snap-top on the surface. The active metal templated rotaxane approach helps in quick and irreversible gate formation for effective utilization of the drug. The folic acid head group bestows targeting capability, specifically to cancer cells. Once nanoparticles enter the cancer cell, controlled release of the cargo is triggered by cleavage of the disulfide bond using an endogenous glutathione stimulus. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in HeLa cells, demonstrating its use as a potential theranostic material.

The oxidation of phenylhydrazine by tyrosinase.

Tyrosinase was found to catalyze the oxidation of phenylhydrazine to phenol in a reaction that did not resemble those typically performed by tyrosinase. The kinetics of this reaction was investigated by measuring the initial velocity of the formation of phenol (25 °C). The values of k cat and K M for the oxidation of phenylhydrazine were obtained as 11.0 s(-1) and 0.30 mM, respectively. The generation of superoxides during the oxidation of phenylhydrazine by tyrosinase was monitored by nitroblue tetrazolium (NBT) assay. In the phenylhydrazine-tyrosinase reaction, 1 mol O2 was required for the production of 1 mol phenol and 1/6 mol superoxide. The decomposition of superoxide by superoxide dismutase enhanced the rate constant of the oxidation of phenylhydrazine. Phenol formed in the oxidation of phenylhydrazine by tyrosinase was further oxidized by tyrosinase to an o-quinone, after the oxidation of phenylhydrazine by tyrosinase was almost completed.