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Innovative Medicines & Omics Antioxidant nanomedicines for therapies

The development of cardiovascular diseases including can accumulate in the cardiac region passively after
myocardial ischemia-reperfusion injury, atherosclerosis, intravenous administration, protecting cardiomyocytes
and aortic aneurysm is closely associated with the against oxidative stress and reducing their apoptosis.
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overexpression of ROS. Antioxidant nanomedicines are In addition, these nanoparticles can also promote the
constructed recently to alleviate cardiovascular oxidative polarization of macrophages from a pro-inflammatory
stress and delay or reverse the progressions of these lethal M1 phenotype to an anti-inflammatory M2 phenotype,
diseases. thus modulating inflammatory microenvironment and
synergistically restoring cardiac function.
3.1. Myocardial ischemia-reperfusion injury
treatment Antioxidant nanocatalysts, such as fullerene and CeO
2
nanoparticles, have also been applied for ROS scavenging
Myocardial infarction is usually known as heart attack during myocardial ischemia-reperfusion injury. 67,68 For
caused by acute occlusion or stenosis of coronary arteries, example, in 2012, Pagliari et al. first evidenced that CeO
2
resulting in sudden ischemia and hypoxia. Reperfusion nanoparticles can protect cardiac progenitor cells from
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through percutaneous coronary intervention is often used oxidative stress. Very recently, Hyeon et al. also reported
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to restore blood supply, which, however, inevitably leads a copper-deposited CeO nanoparticle, which presents
to myocardial ischemia-reperfusion injury, during the an elevated antioxidative property over pristine CeO
2
period plenty of ROS are produced in cardiomyocytes, nanoparticle. Animal model of myocardial infarction
2
68
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causing oxidative damage. In addition, the oxidative indicated that the engineered nanoparticle could promote
stress will also activate immune system to trigger a severe the polarization of macrophages toward M2 phenotype,
inflammatory response, which further promotes ROS presenting desirable anti-inflammation property in
generation, forming a vicious circle, finally deteriorating myocardial tissues.
cardiac function. 57,58 To alleviate myocardial oxidative
stress and protect cardiomyocytes, molecular antioxidants, 3.2. Cardioprotection from chemodrugs
such as Vitamin C, Vitamin E, and N-acetylcysteine, are Chemodrug doxorubicin (DOX) (or adriamycin) has
used to scavenge intramyocardial excessive ROS. 59,60 As been extensively used in cancer treatment. However,
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these molecules are administrated intravenously, they are this chemodrug can lead to serious cardiotoxicity
vulnerable to oxidation and/or clearance during blood and subsequent cardiomyopathy, by promoting the
circulation, compromising therapeutic efficacy, which overproduction ROS in cardiomyocytes. 71,72 Oon binding
will necessitate enhanced doses of administration, and to intracellular DNA, DOX is reduced to semiquinone that
resulting in side effects. can further react with O to form O and H O . Excessive
•−
71
2
2
2
2
Nanocarriers have been used to load antioxidants Fe are also generated in cardiomyocytes to catalyze H O
2+
2
2
for favoring the treatment of myocardial ischemia- into •OH, triggering a significant oxidative damage, which
reperfusion injury. In 2015. Hardy et al. prepared leads to cardiomyocyte ferroptosis. Although various
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poly(glycidyl methacrylate) nanoparticles to load nanocarriers have been used to deliver DOX, the side
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curcumin or resveratrol, for relieving oxidative stress effect, especially cardiotoxicity is still distinct. 75
in cardiomyocytes. Recently, Guo et al. also used MOF Park et al. prepared a polyoxalate nanoparticle
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nanoparticles to deliver SOD to myocardial region. This encapsulating vanillyl alcohol, an antioxidative component
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nanosystem can reduce cardiomyocyte death and alleviate of herb Gastrodia elata, for alleviating DOX-induced
inflammation, thereby mitigating myocardial injury. cardiomyopathy. However, this work is not able to scavenge
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Nanomaterials with intrinsic antioxidative activities excessive Fe ions in cardiomyocyte. Very recently, our group
have also been applied to scavenge intramyocardial ROS. has reported a magnesium hexacyanoferrate nanoparticle,
Melanin is a typical natural pigment in human, whose which can undergo ion-exchange reaction in DOX-
main component is polydopamine with a broad-spectrum contaminated pathological cardiac microenvironment
ROS-scavenging property. Zhou et al. prepared melanin to fix excessive Fe ions by substituting for Mg , forming
2+
63
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nanoparticles and integrated them within alginate Prussian blue nanocatalysts in situ (Figure 5). Prussian
hydrogel for facilitating myocardial repair. Following this blue is a typical antioxidative agent with SOD and catalase-
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work, Mo et al. prepared allomelanin nanoparticles (with like activities, capable of catalyzing the disproportionation
31
similar composition to melanin ) to ameliorate oxidative reactions of O and H O , therefore scavenging ROS
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•−
2
2
2
stress in myocardial microenvironment (Figure 4). Due efficiently. In vitro high throughput mRNA sequencing
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to the enhanced vascular permeability during myocardial and in vivo echocardiography evaluation demonstrated
ischemia-reperfusion injury, allomelanin nanoparticles the desirable cardioprotective effects of the as-prepared
Volume 1 Issue 1 (2024) 5 doi: 10.36922/imo.2527