Page 32 - IMO-1-1

Innovative Medicines & Omics Antioxidant nanomedicines for therapies

macrophages and promote inflammation, during which 8. Liver disease treatment
resident fibroblasts and epithelial cells differentiate into
myofibroblasts, secreting autocrine pro-fibrotic mediators Liver is the main metabolism and detoxification organ of
that aggravate extracellular matrix accumulation, body. It has been well-documented that the intravenously
resulting in pulmonary fibrosis, which severely diminishes administered nanoparticles will be nonspecifically
captured by mononuclear phagocyte systems, especially
respiratory function. 302,303 Till now, only pirfenidone is macrophages (Kupffer cells) and liver sinusoidal
approved for clinical treatment of pulmonary fibrosis
in European Union and Japan, but the therapeutic endothelial cells in liver, to remove them from blood
314-316
efficacy is not significant. Due to the oxidative stress- circulation. This is a key difficulty for nanomedicines
304
to treat various diseases especially cancer, but is an innate
associated mechanism of pulmonary fibrosis, antioxidant biological advantage for treating liver diseases by favoring
N-acetylcysteine has also been used in combination with nanomedicine accumulation in hepatic pathological
prednisone for elevating therapeutic efficacy.
regions. Due to the increased unhealthy lifestyle of modern
The development of antioxidant nanomedicines has people, it was predicted that over two million people died
provided new strategies for treating pulmonary fibrosis. of liver diseases each year. Antioxidant nanomedicines
305
317
Nagao et al. prepared nanoliposomes with similar structures capable of mitigating hepatic oxidative stress has attracted
to natural red blood cells, for delivering antioxidative gas attention from nanomedical field recently.
carbon monoxide to pulmonary regions. In a bleomycin-
306
induced pulmonary fibrosis mice model, the gas delivery 8.1. Hepatic ischemia-reperfusion injury treatment
system was demonstrated to be capable of suppressing During liver surgery such as liver resection and
pulmonary fibril formation and improving respiratory transplantation, temporary blockage of blood flow is
function. Keum et al. prepared nanoparticles composed necessary to prevent bleeding, which, however, inevitably
of bilirubin, an endogenous antioxidative bile acid, for results in hepatic ischemia. Paradoxically, when the
307
318
treating pulmonary fibrosis. In vivo results indicate blood supply and oxygen delivery are normalized after
308
that the nanomedicine can attenuate the ROS-triggered surgery, a second ischemia-reperfusion injury will occur,
pathological cascade of pulmonary fibrosis, providing a during which excessive ROS are produced to exacerbate
prophylactic anti-fibrotic therapeutic option. hepatic inflammation, promoting the secretion of pro-
inflammatory cytokines including TNF-α, IL-6, and
7.3. Asthma treatment
IL-1β and damaging the function of liver, and eventually
Heavy cigarette smokers or people under frequent resulting in acute liver injury or failure. 319-321 Till now,
exposure to environmental pollutants are prone to no pharmaceutical intervention has been approved for
development of chronic inflammatory airway diseases treating hepatic ischemia-reperfusion injury.
such as asthma, which results from ROS overproduction Antioxidant nanomedicines were used to mitigate
in the lung in response to exogenous factors. 309,310 hepatic oxidative stress and regulate inflammatory
Oxidative stress further leads to acute inflammation and microenvironment of hepatic region. Kim et al. indicated
lung dysfunction characteristic of airflow obstruction, that bilirubin nanoparticle preconditioning can protect
airway hyperresponsiveness, and remodeling. Due to a the liver against ischemia-reperfusion injury. 322 Jun g et al.
large population of cigarette smokers and the increasingly constructed a nanomedicine self-assembled from all-
deteriorating environmental pollution, 300 million trans retinoic acid, a natural derivative of Vitamin A
individuals globally suffer from asthma. The inhaled with antioxidant activity, for ischemia-reperfusion injury
311
corticosteroids were used in clinic for treating asthma, mitigation. In a mouse model of hepatic ischemia-
323
but the side effect is distinct. To solve this issue, Kim reperfusion injury, the nanomedicine can protect liver
312
et al. prepared a bilirubin-based nanoparticle to scavenge effectively from oxidative stress and inhibit the expression
pulmonary excessive ROS for asthma treatment. The of pro-inflammatory factors such as TNF-α, IL-1β, and
313
antioxidative property of bilirubin nanoparticle further IL-6. Inorganic nanocatalysts, such as CeO , have also
2
promotes immunoregulations such as reduction of been applied in treating hepatic ischemia-reperfusion
type 2 T-helper cell populations, a key type of cells in the injury by initiating catalytic ROS-scavenging reactions.
pathogenesis of asthma, finally allieviating the symptoms. Manne et al. revealed that prophylactic treatment
Current application of antioxidant nanomedicines in with CeO nanoparticles can protect hepatocytes from
2
the treatment of lung diseases is still in its infancy (Table 5). oxidative stress and inhibit the secretion of inflammatory
It is expected that more antioxidative nanomedicines will factors in a Sprague-Dawley rat model. Ni et al. also
324
be developed in the future for treating lung diseases. demonstrated that CeO nanoparticles can effectively
2
Volume 1 Issue 1 (2024) 26 doi: 10.36922/imo.2527