Biosynthetic Mechanism of Luminescent ZnO Nanocrystals in the Mammalian Blood Circulation and Their Functionalization for Tumor Therapy.

The biosynthesis of nanoparticles in bioreactors using microbial, plant, or animal cells is at the forefront of nanotechnology. We demonstrated for the first time that luminescent, water-soluble ZnO nanocrystals (bio-ZnO NCs) can be spontaneously biosynthesized in the mammalian blood circulation, not in cells, when animals were fed with Zn(CH3COO)2 aqueous solution. Serum albumin, rather than metallothioneins or glutathione, proved to play the pivotal role in biosynthesis. The bio-ZnO NCs were gradually taken up in the liver and degraded and excreted in the urine. Thus, we propose that in mammals such as rodents, bovinae, and humans, excess metal ions absorbed into the cardiovascular system via the intestine can be transformed into nanoparticles by binding to serum albumin, forming a "provisional metal-pool", to reduce the toxicity of free metal ions at high concentration and regulate metal homeostasis in the body. Furthermore, the bio-ZnO NCs, which showed favorable biocompatibility, were functionalized with the anticancer drug daunorubicin and effectively achieved controlled drug release mediated by intracellular glutathione in tumor xenograft mice.