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Innovative Medicines & Omics Antioxidant nanomedicines for therapies

nanoparticles of only 3 nm that enables repeated topical (Figure 25). The nanocatalyst presents excellent catalase-
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administrations of the nanocatalyst. These ultrasmall like activity, whose Michaelis–Menten constant (K ) is
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M
nanoparticles can penetrate through cornea and aqueous superior to that of natural catalase. In oxygen-induced
humor to reach the retina, and both DKOrd8 mouse retinopathy mouse model and laser-induced choroidal
model (dry AMD model) and laser-induced choroidal neovascularization mouse model, the single-atom iron
neovascularization mouse model (wet AMD model) nanocatalyst was evidenced to suppress pathological
demonstrated that the eye drop solution can alleviate angiogenesis and promote vascular normalization. In
retinal degeneration. addition to these nanocatalysts, ferrihydrite has also been
reported with catalase-like activity. It is expected that
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As a natural antioxidant, melanin also exists in retinal such a nanocatalyst can also be used for treating retinal
pigment epitheliums, protecting these cells against oxidative neovascularization.
stress. However, it cannot be synthesized naturally by
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retinal pigment epitheliums, and the cytoprotective effect 9.3. Glaucoma treatment
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declines with age, thereby promoting AMD progression. Glaucoma is a chronic ocular disorder and the second
To address this issue, Kwon et al. prepared PEGylated leading cause of blindness. It is initiated by elevated
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melanin-like nanoparticles and supplement them in the intraocular pressure that leads to ischemia-reperfusion
retina through intravitreal injection. These nanoparticles injury, during which the overproduction of ROS will
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can accumulate in retinal pigment epitheliums and damage optic nerves and lead to vision loss. To scavenge
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further locate in cytosol for at least 3 months after a ROS for alleviating glaucomatous damage, antioxidant
single intravitreal injection, capable of mitigating macular α-lipoic acid has been used in glaucoma treatment
oxidative stress efficiently. through dietary supplementation, but the efficacy is
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9.2. Retinal neovascularization treatment unsatisfactory. Luo et al. prepared a CeO nanoparticle-
2
based eye drop for glaucoma therapy. In this work, the
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Neovascularization of retina is a biological basis for the nanoparticles were functionalized with chitosan, which
progression of various retinal diseases, such as retinopathy can open the tight junctions in corneal epithelium,
of prematurity, AMD, and diabetic retinopathy, 370-372 leading enabling the accumulation of nanoparticles in the ciliary
to severe symptoms such as retinal edema, detachment, body to scavenge ROS. Single topical instillation of the
and even vision loss. Hypoxia plays an important antioxidative eye drop on glaucomatous eyes of rabbit
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role in the occurrence of retinal neovascularization by models resulted in mitigated disease symptoms for 7 days,
promoting VEGF expression. Hypoxia also favors showing great promise for treating glaucoma.
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the production of ROS, leading to oxidative damage Although several antioxidant nanomedicines have
to retina. Therefore, to suppress or reverse retinal been used for ophthalmologic applications (Table 7), the
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neovascularization, the concurrent oxygenation and pharmacokinetics and degradability of nanomedicines in
ROS scavenging are highly desired to alleviate both eye should be investigated comprehensively to guarantee
hypoxia and oxidative stress. Current strategies for retinal their long-term safety, given complex structure of the eye,
neovascularization management, especially anti-VEGF as well as high sensitivity of inner optic nerves. 387
agents (e.g., ranibizumab, aflibercept, and bevacizumab),
only show a moderate therapeutic efficacy. 376-378 10. Intestinal disease treatment
The catalase in nature can catalyze H O into O , which Gastrointestinal tract is prone to suffer from inflammation
2
2
2
can address hypoxia and oxidative stress concurrently. during the constant contacting to external ingested
Several antioxidant nanocatalysts possessing catalase- substances. Inflammatory bowel disease is a family
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like activity have recently been applied for treating of chronic and idiopathic intestinal disorders including
retinal neovascularization. Xue et al. used liposomes to ulcerative colitis and Crohn’s disease. Although
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encapsulate Pt nanoparticles, followed by modification inflammatory bowel disease does not result in high
with triphenyl phosphonium that can promote the mortality, it does significantly influence the quality of
accumulation of nanomedicine in mitochondria of retinal patients’ life. The overexpression of ROS by inflammatory
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endothelial cells. Pt nanoparticles with intrinsic catalase- cells is a key pathogenic factor of inflammatory bowel
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like activity can catalyze cellular H O into O , alleviating disease, directly damaging intestinal epithelial cells to
2
2
2
both hypoxia and oxidative stress, finally restraining retinal trigger intestinal mucosa injury, and further exacerbating
neovascularization, as demonstrated in an oxygen-induced inflammatory responses. In addition, oxidative stress
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retinopathy mouse model. Recently, Zhang et al. prepared can also lead to dysbiosis of gut microbiota. Although
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a single-atom iron nanocatalyst with defective Fe–N sites several anti-inflammatory agents such as infliximab
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Volume 1 Issue 1 (2024) 31 doi: 10.36922/imo.2527