- Novel nanostructures called DNA origami
nanostructures (DONs) have been developed using the latest nanotechnology
- Imaging studies using positron emission tomography
(PET) have shown that when these DONs are injected, they preferentially
accumulate in the kidneys
- Acute kidney injury (AKI) can be caused by
oxidative stress. The DONs, accumulated in the kidneys, can counteract the
oxidative stress, thereby preventing the onset of AKI in healthy kidneys
or treating AKI in diseased kidneys
A novel method for
treating and preventing acute kidney injury (AKI) was developed using
self-assembling nanomaterials. These
nanomaterials are suitable for use in living systems due to their stability,
low toxicity, and low immunogenicity. However, this has so far not been
possible, but this new study has made major headway in this direction and the study was published in Nature
Biomedical Engineering, a Springer Nature publication.
Acute kidney injury (AKI), formerly known as acute
renal failure is a serious condition in which the kidneys shut-down abruptly,
leading to a rapid build-up of nitrogenous waste and reduced urine production.
This can occur within hours or days of onset of disease, which often leads to
various complications. In advanced stages of AKI, kidney transplantation may be
required as well as supportive treatment measures such as rehydration and hemodialysis.
‘Novel nanostructures have been developed using new nanotechnology methods. Oxidative stress, which causes acute kidney injury (AKI), can be neutralized by these nanostructures. This can help in preventing AKI in healthy kidneys and treating AKI in diseased ones.’
13.3 million new AKI cases are reported annually, with 1.7 million deaths. Therefore,
protecting healthy kidneys from injury and treating those already injured is a
major medical challenge. Currently, there is no cure for AKI.
What is Nanotechnology and Nanomedicine?
- Nanotechnology: Thisis the branch of technology that deals with dimensions and
tolerances of less than 100 nanometers (nm), especially the manipulation
of individual atoms and molecules.
- Nanomedicine: This involves the engineering of atoms
and molecules at the nano-level for developing medical applications. This
is a new and exciting area of biomedical research and has opened hitherto
unexplored areas such as advanced imaging and therapeutic strategies
against various diseases, including AKI.
have a variety of shapes, including tubular, triangular or rectangular and are
made by a method called DNA origami. Here, the base-pairing properties of the
four DNA bases are exploited to engineer DNA origami nanostructures
(DONs). These DONs are capable of self-assembling and when introduced into living
systems, they preferentially accumulate in the kidneys.
The study was led
by Dr. Hao Yan, Milton D. Glick Distinguished Professor and Director, Center
for Molecular Design and Biomimetics, Arizona State University, USA. Dr. Yan’s
collaborator was Dr. Weibo Cai, Vilas Distinguished Achievement Professor,
University of Wisconsin-Madison, USA.
“The interdisciplinary collaboration between
nanomedicine and the in-vivo imaging team led by Professor Weibo Cai at the
University of Wisconsin-Madison and the DNA nanotechnology team has led to a
novel application – applying DNA origami nanostructures to treat acute kidney
injury,” says Professor Yan. “This represents a new horizon for DNA
The study was
carried out in mice and in cell culture, using human embryonic kidney (HEK)
cells. Kidney function in mice was assessed by measuring the levels of serum
creatinine and blood urea nitrogen (BUN). The safety of the DONs was
established by evaluating their potential to elicit an immune response in mice
by measuring the levels of interneukin-6 (IL-6) and tumor necrosis factor-α
(TNF-α). These immunogenicity studies revealed that the DONs were not
immunogenic. Moreover, histologic staining of vital organs such as the heart, liver,
lungs, spleen, and kidneys indicated that they had very low toxicity. These
features make DONs attractive therapeutic agents for clinical studies in
Professor Yan and
his team engineered all three types of DONs (tubular, triangular, and
rectangular shaped). These were radio-labeled for studying their behavior in
mice kidneys by using positron emission tomography (PET)
imaging. The PET scans revealed that the DONs accumulated in the
kidneys of both healthy mice, as well as those suffering from AKI. Furthermore,
of the three shapes of DONs used in the study, the rectangular shaped DONs
exhibited a superior therapeutic potential than the others. Their efficacy was
comparable to the antioxidant drug, N-acetylcysteine (NAC), which is currently
regarded as the “Gold Standard” for the treatment of AKI.
Mechanism of Action of DONs
It is well
established that oxidative stress, https://www.medindia.net/patientinfo/oxidative-stress-free-radicals-cell-injury.htm
About Oxidative Stress / Free Radicals Cell
Injury mediated by reactive oxygen species (ROS), is a major factor in the
pathogenesis of AKI. In the present study, the observed protective and
therapeutic benefits of DONs were due to their ability to scavenge these ROS.
This protects susceptible kidney cells from oxidative damage. These studies,
carried out in HEK cells subjected to ROS, showed that the DONs could
counteract the oxidative stress within two hours of incubation with these
affected human kidney cells.
What is the Importance of the Study?
This is the first
study to use DONs within living systems, using quantitative imaging to track
their behavior. PET imaging allowed for real-time monitoring of the circulation
of these DONs within the living organism and for assessing their physiological
distribution. PET revealed that the accumulation of the rectangular shaped DONs
in the kidneys was comparatively much higher than the other DONs, and therefore
proved to be most effective for treating AKI in mice. This opens new avenues
for the development of novel therapeutic strategies for the treatment of AKI as
well as other kidney diseases.
In this regard,
Professor Cai said: “This is an excellent example of team science, with multidisciplinary
and multinational collaboration.The four research groups are located in
different countries, but they communicate regularly and have synergistic
expertise. The three equally-contributing first authors (Dawei Jiang, Zhilei
Ge, Hyung-Jun Im) also have very different backgrounds, one in radiolabeling
and imaging, one in DNA nanostructures, and the other in clinical nuclear
medicine. Together, they drove the project forward.”
The study establishes
the ability of DONs to confer localized protection to kidneys from AKI, based
on their effective ROS scavenging ability in both HEK cell culture and in
living mouse kidneys. It is, therefore, plausible that these therapeutic
benefits could be extended to kidneys already damaged by AKI or other kidney
study opens-up new possibilities for the development of novel therapeutic
strategies using programmable nanostructures that can be engineered for a
variety of applications, including targeted drug delivery and tissue repair,
- DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury – ((http://dx.doi.org/10.1038/s41551-018-0317-8))