Unexpected intracellular biodegradation and recrystallization of gold nanoparticles

Gold nanoparticles are used in an expanding spectrum of biomedical
applications. However, little is known about their long-term
fate in the organism as it is generally admitted that the inertness
of gold nanoparticles prevents their biodegradation. In this
work, the biotransformations of gold nanoparticles captured by
primary fibroblasts were monitored during up to 6 mo. The combination
of electron microscopy imaging and transcriptomics study
reveals an unexpected 2-step process of biotransformation. First,
there is the degradation of gold nanoparticles, with faster disappearance
of the smallest size. This degradation is mediated by
NADPH oxidase that produces highly oxidizing reactive oxygen
species in the lysosome combined with a cell-protective expression
of the nuclear factor, erythroid 2. Second, a gold recrystallization
process generates biomineralized nanostructures consisting
of 2.5-nm crystalline particles self-assembled into nanoleaves.
Metallothioneins are strongly suspected to participate in buildings
blocks biomineralization that self-assembles in a process
that could be affected by a chelating agent. These degradation
products are similar to aurosomes structures revealed 50 y
ago in vivo after gold salt therapy. Overall, we bring to light
steps in the lifecycle of gold nanoparticles in which cellular pathways
are partially shared with ionic gold, revealing a common
gold metabolism.