Quantum dots as phototoxic drugs and sensors of specific metabolic processes in living cells.

Abstract

When conjugated to CdSe/ZnS nanocrystals (quantum dots), the nucleobase adenine and the neurotransmitter dopamine quench fluorescence emission from in a manner strongly dependent upon the size of the quantum dot. The degree of quenching serves to predict the efficiency with which the conjugates are able to enter living cells. Along with quenching, the presence of specific receptors on the cells is necessary for QD binding, entry, and phototoxicity. Toxicity is manifested by opening of large membrane pores and by oxidative DNA damage, and does not require the release of Cd+2. In bacterial cells, light exposure is necessary for uptake, and procedures to reduce toxicity eliminate labeling. In mammalian cells, antioxidants prevent toxicity but not QD uptake, leading to QD-loaded cells that are nonfluorescent before light exposure. These findings provide a general procedure for rational design of nanoparticle-based photosensitizing drugs and for "off-on" fluorescent labels.