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Innovative Medicines & Omics Antioxidant nanomedicines for therapies

magnesium hexacyanoferrate nanoparticles, indicating its M1 macrophage, 97,98 the nanoparticles can target plaque
feasibility for detoxication after DOX administration. This region efficiently, thus presenting desirable therapeutic
study addresses both oxidative stress and excessive Fe ions effect. Prussian blue nanoparticles and Pt nanoparticles
in cardiomyocytes, providing an applicable strategy for have also been demonstrated to be capable of alleviating
cardioprotection. inflammation in atherosclerotic region. 99,100

3.3. Atherosclerosis treatment The efficient treatment of atherosclerosis necessitates not
only the modulation of inflammatory microenvironment,
Atherosclerosis is a chronic inflammatory disease of the but also the clearance of excessive lipid in atherosclerotic
arterial wall with aberrant lipid accumulation, which is plaque. Autophagy is a self-protective process of cells,
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closely associated with various cardiovascular abnormities during which cytoplasmic indispensable constituents
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such as myocardial infarction. The pathophysiology of are captured by autophagosomes to deliver them to
atherosclerotic lesion formation is mostly from aging- lysosomes for degradation, promoting the metabolism of
related endothelial injury that promotes low-density biomacromolecules including lipid. 101-103 Research showed
lipoprotein (LDL) entry and retention in subendothelial that macrophage autophagy can promote cholesterol efflux
space. ROS is generated in the region consequently, to inhibit foam cell formation. It is conceived that by
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leading to the endothelial dysfunction and oxidative promoting macrophage autophagy, the lipid metabolism
modification of LDL (ox-LDL). Macrophages phagocytize can be promoted to stabilize the atherosclerotic
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ox-LDL particles and form foam cells, forming a plaque plaque. Wu et al. fabricated trehalose nanoparticles
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microenvironment. As oxidative stress is a key pathogenic by loading L-arginine and phosphatidylserine to target
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factor of atherosclerosis, scavenging excessive ROS is macrophages in the plaque and treat atherosclerosis
beneficial to delay disease progression. Several molecular (Figure 6). Phosphatidylserine was reported to be
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antioxidants have been applied for atherosclerosis therapy, easily taken up by macrophages, targeting macrophages
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including coenzyme Q10, Vitamins E and C, probucol, favorably. L-arginine can react with H O in pathological
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proanthocyanidin, and tempol (TP). However, the low microenvironment to produce nitric oxide (NO). The
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accumulation efficiency and low stability restrict their H O consumption facilitates inflammation alleviation,
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further application in clinic. 88 while the produced NO promotes the proliferation of
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Various nanomedicines with diversified chemical vascular endothelial cells. In addition, trehalose is a
properties have been constructed for atherosclerosis mammalian target of rapamycin (mTOR)-independent
treatment. 89-92 It is noted that due to the leaky vascular autophagy inducer that activates macrophage autophagy.
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structure in atherosclerotic plaque region, nanomedicines Cellular and in vivo experiments further evidenced the
can accumulate passively at pathological site by anti-atherosclerotic effect of the nanomedicine. Recently,
extravasation from blood capillary through the enhanced Hu et al. also prepared a macrophage-coated tetrapod PdH
permeation and retention (EPR) effect. 93,94 Nanoparticles nanoparticle, which can not only target atherosclerotic
could be modified with targeting ligand to facilitate their plaque, but also scavenge ROS efficiently by releasing
accumulation in vascular endothelium. In addition, antioxidative H and generating Pd antioxidant catalyst
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immune cells in the pathological regions also favor the as well. Importantly, the distinct tetrapod needle-like
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entrance of nanomedicines to atherosclerotic plaques. morphology of PdH nanoparticle favors the autophagy of
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Therefore, antioxidant nanomedicines can arrive at macrophages, enhancing the anti-atherosclerotic effect.
atherosclerotic plaque to initiate antioxidative therapeutic It is expected that more advanced nanomedicines will be
effect. Wang et al. prepared cyclic polysaccharide developed in the future to eliminate atherosclerotic plaque
β-cyclodextrin nanoparticles containing TP and and restore vascular function.
phenylboronic acid pinacol ester, which can scavenge O
•−
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and H O , respectively. The antioxidant nanomedicine 3.4. Peripheral arterial disease treatment
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enables inflammation mitigation and foam cell Peripheral arterial disease is an atherosclerosis-related
formation inhibition, finally regulating the pathological pathological abnormality characterized by artery
microenvironment. Du et al. used hyaluronic acid to guide obstruction in hindlimb, leading to limb ischemia. This
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the assembly of CeO nanoparticles and used them for disease has now aroused extensive attention due to the
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anti-atherosclerotic therapy. Hyaluronic acid can not only increasing number of elders suffering from the disease.
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improve the stability and biocompatibility of nanoparticle, During ischemia, excessive ROS are produced, promoting
but also increase the amount of Ce in CeO , significantly inflammation and vascular damage. 114,115 Therefore, ROS
3+
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elevating the SOD-like activity. In addition, due to the scavenging may achieve efficient treatment of peripheral
affinity of hyaluronic acid toward pro-inflammatory arterial disease. Several antioxidants, such as Vitamin E,
Volume 1 Issue 1 (2024) 7 doi: 10.36922/imo.2527