Nanoparticles
have been around for many years but we are still, as a species, just scratching
at the surface of understanding them. Of course, the surface is the most
important part of a nanoparticle since, due to their incredibly small size,
they have an incredible surface area to volume ratio. For example, 1g of PLGA
nanoparticles (100 nm) would have a surface area of 7.8 square meters (a little
larger than a typical parking space for a car). For this reason, the surface
and how it interacts with living organisms is the most important aspect of
nanoparticle technology. Recently, Angie (Morris) Thorn at University of Iowa published
a PhD thesis which details efforts to broaden our understanding of nanoparticle
surface interactions with cells. This includes work with PLGA-NH2 (PolyVivo
AI063) from PolySciTech (www.polyscitech.com)
to generate nanoparticles covered with either chitosan (for mucoadhesion) or
TPP (mitochondria-targeting) to create targeted nanoparticles as drug-delivery
vectors. Read more: Thorn, Angie
Sue Morris. "The impact of nanoparticle surface chemistry on biological
systems." (2017). http://ir.uiowa.edu/etd/5659/
“Abstract: The unique properties of nanomaterials, such as their small
size and large surface area-to-volume ratios, have attracted tremendous
interest in the scientific community over the last few decades. Thus, the
synthesis and characterization of many different types of nanoparticles has
been well defined and reported on in the literature. Current research efforts
have redirected from the basic study of nanomaterial synthesis and their
properties to more application-based studies where the development of
functionally active materials is necessary. Today such nanoparticle-based
systems exist for a range of biomedical applications including imaging, drug
delivery and sensors. The inherent properties of the nanomaterial, although
important, aren’t always ideal for specific applications. In order to optimize
nanoparticles for biomedical applications it is often desirable to tune their
surface properties. Researchers have shown that these surface properties (such
as charge, hydrophobicity, or reactivity) play a direct role in the interactions
between nanoparticles and biological systems can be altered by attaching
molecules to the surface of nanoparticles. In this work, the effects of
physicochemical properties of a wide variety of nanoparticles was investigated
using in vitro and in vivo models. For example, copper oxide (CuO)
nanoparticles were of interest due to their instability in biological media.
These nanoparticles undergo dissolution when in an aqueous environment and tend
to aggregate. Therefore, the cytotoxicity of two sizes of CuO NPs was evaluated
in cultured cells to develop a better understanding of how these propertied
effect toxicity outcomes in biological systems. From these studies, it was
determined that CuO NPs are cytotoxic to lung cells in a size-dependent manner
and that dissolved copper ions contribute to the cytotoxicity however it is not
solely responsible for cell death. Moreover, silica nanoparticles are one of
the most commonly used nanomaterials because they are easy to synthesize and
their properties (such as size, porosity and surface chemistry) can be
fine-tuned. Silica nanoparticles can be found in thousands of commercially
available products such as toothpastes, cosmetics and detergents and are
currently being developed for biomedical applications such as drug delivery and
biomedical imaging. Our findings herein indicate that the surface chemistry of
silica nanoparticles can have an effect on lung inflammation after exposure.
Specifically, amine-modified silica NPs are considered to be less toxic compared
to bare silica nanoparticles. Together, these studies provide insight into the
role that material properties have on toxicity and allow for a better
understanding of their impact on human and environmental health. The final aim
of this thesis was to develop surface-modified nanoparticles for drug delivery
applications. For this, biodegradable, polymeric NPs were used due to their
inert nature and biocompatibility. Furthermore, polymeric NPs are excellent for
loading drugs and using them as drug delivery vehicles. In this work, poly
(lactic-co-glycolic acid) (PLGA) NPs were loaded with a therapeutic peptide.
These NPs were then coated with chitosan (a mucoadhesive polymer) for the
treatment of allergic asthma or coated with a small cationic mitochondrial targeting
agent for the treatment of ischemia/reperfusion injury. Taken as a whole, this
thesis sheds light on the impact of NPs on human health. First by providing
useful toxological data for CuO and silica NPs as well as highlighting the
potential of surface-modified polymeric NPs to be used in drug delivery-based
applications. Keywords: Cell Culture, Nanoparticle, Toxicity”
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