We have discovered functionalized multiwalled carbon nanotubes with reduced protein-binding, cytotoxicity, and immune response and the associated structure-activity relationships using in silico surface molecular diversity design, combinatorial library synthesis, and multiple biological screenings. Our results demonstrated the general utility of the nanocombinatorial library approach in nanomedicine and nanotoxicity research.
Airborne
particular matter (PM2.5) contains complex
mixtures of pollutants, and their compositions also vary with time
and location. Inhalation of PM2.5 may cause a number of
diseases, such as bronchial and lung inflammation and lung cancer.
So far, how different components of PM2.5 contribute to
inflammation and toxicity is still not known. To identify key PM2.5 components that are responsible for inflammation, here
we took a reductionism approach and synthesized a model PM2.5 library containing 20 carbon nanoparticle based members with loadings
of As(III), Pb2+, Cr(VI), and BaP individually or in combination
at environment relevant concentrations. We discovered that only carbon
nanoparticle–Pb2+ adducts, not other pollutants
or adducts, induced inflammation in human bronchial cells by suppressing
the expression of a novel long noncoding RNA lnc-PCK1-2:1, while lnc-PCK1-2:1 routinely plays a regulatory
role in inhibiting inflammation. This finding was further substantiated
by varying Pb2+ loadings on carbon nanoparticles and overexpressing lnc-PCK1-2:1. The success of this approach opens an avenue
for further elucidation of molecular mechanisms of PM2.5-induced inflammation and toxicity.
The application of nanoparticles in consumer products and nanomedicines has increased dramatically in the last decade. Concerns for the nano-safety of susceptible populations are growing. Due to the small size, nanoparticles have the potential to cross the placental barrier and cause toxicity in the fetus. This review aims to identify factors associated with nanoparticle-induced fetotoxicity and the mechanisms involved, providing a better understanding of nanotoxicity at the maternal–fetal interface. The contribution of the physicochemical properties of nanoparticles (NPs), maternal physiological, and pathological conditions to the fetotoxicity is highlighted. The underlying molecular mechanisms, including oxidative stress, DNA damage, apoptosis, and autophagy are summarized. Finally, perspectives and challenges related to nanoparticle-induced fetotoxicity are also discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.