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Understanding Nanoparticle Toxicity Mechanisms To Inform Redesign Strategies To Reduce Environmental Impact
journal contribution
posted on 2019-06-03, 14:36 authored by Joseph
T. Buchman, Natalie V. Hudson-Smith, Kaitlin M. Landy, Christy L. HaynesConspectusThere has been a surge of consumer products that incorporate nanoparticles,
which are used to improve or impart new functionalities to the products
based on their unique physicochemical properties. With such an increase
in products containing nanomaterials, there is a need to understand
their potential impacts on the environment. This is often done using
various biological models that are abundant in the different environmental
compartments where the nanomaterials may end up after use.Beyond
studying whether nanomaterials simply kill an organism,
the molecular mechanisms by which nanoparticles exhibit toxicity have
been extensively studied. Some of the main mechanisms include (1)
direct nanoparticle association with an organism’s cell surface,
where the membrane can be damaged or initiate internal signaling pathways
that damage the cell, (2) dissolution of the material, releasing toxic
ions that impact the organism, generally through impairing important
enzyme functions or through direct interaction with a cell’s
DNA, and (3) the generation of reactive oxygen species and subsequent
oxidative stress on an organism, which can also damage important enzymes
or an organism’s genetic material. This Account reviews these
toxicity mechanisms, presenting examples for each with different types
of nanomaterials.Understanding the mechanism of nanoparticle
toxicity will inform
efforts to redesign nanoparticles with reduced environmental impact.
The redesign strategies will need to be chosen based on the major
mode of toxicity, but also considering what changes can be made to
the nanomaterial without impacting its ability to perform in its intended
application. To reduce interactions with the cell surface, nanomaterials
can be designed to have a negative surface charge, use ligands such
as polyethylene glycol that reduce protein binding, or have a morphology
that discourages binding with a cell surface. To reduce the nanoparticle
dissolution to toxic ions, the toxic species can be replaced with
less toxic elements that have similar properties, the nanoparticle
can be capped with a shell material, the morphology of the nanoparticle
can be chosen to minimize surface area and thus minimize dissolution,
or a chelating agent can be co-introduced or functionalized onto the
nanomaterial’s surface. To reduce the production of reactive
oxygen species, the band gap of the material can be tuned either by
using different elements or by doping, a shell layer can be added
to inhibit direct contact with the core, or antioxidant molecules
can be tethered to the nanoparticle surface. When redesigning nanoparticles,
it will be important to test that the redesign strategy actually reduces
toxicity to organisms from relevant environmental compartments. It
is also necessary to confirm that the nanomaterial still demonstrates
the critical physicochemical properties that inspired its inclusion
in a product or device.