Glycol Chitosan Engineered Autoregenerative Antioxidant Significantly Attenuates Pathological Damages in Models of Age-Related Macular Degeneration

Rajendra N. Mitra, Ruijuan Gao, Min Zheng, Ming Jing Wu, Maxim A. Voinov, Alex I. Smirnov, Tatyana I. Smirnova, Kai Wang, Sai Chavala, Zongchao Han

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Age-related macular degeneration (AMD) is the foremost cause of irreversible blindness in people over the age of 65 especially in developing countries. Therefore, an exploration of effective and alternative therapeutic interventions is an unmet medical need. It has been established that oxidative stress plays a key role in the pathogenesis of AMD, and hence, neutralizing oxidative stress is an effective therapeutic strategy for treatment of this serious disorder. Owing to autoregenerative properties, nanoceria has been widely used as a nonenzymatic antioxidant in the treatment of oxidative stress related disorders. Yet, its potential clinical implementation has been greatly hampered by its poor water solubility and lack of reliable tracking methodologies/processes and hence poor absorption, distribution, and targeted delivery. The water solubility and surface engineering of a drug with biocompatible motifs are fundamental to pharmaceutical products and precision medicine. Here, we report an engineered water-soluble, biocompatible, trackable nanoceria with enriched antioxidant activity to scavenge intracellular reactive oxygen species (ROS). Experimental studies with in vitro and in vivo models demonstrated that this antioxidant is autoregenerative and more active in inhibiting laser-induced choroidal neovascularization by decreasing ROS-induced pro-angiogenic vascular endothelial growth factor (VEGF) expression, cumulative oxidative damage, and recruitment of endothelial precursor cells without exhibiting any toxicity. This advanced formulation may offer a superior therapeutic effect to deal with oxidative stress induced pathogeneses, such as AMD.

Original languageEnglish
Pages (from-to)4669-4685
Number of pages17
JournalACS Nano
Volume11
Issue number5
DOIs
StatePublished - 23 May 2017

Fingerprint

Oxidative stress
degeneration
antioxidants
Glycols
Antioxidants
Chitosan
glycols
damage
pathogenesis
Water
Reactive Oxygen Species
solubility
Solubility
cumulative damage
blindness
disorders
water
angiogenesis
Oxygen
oxygen

Keywords

  • age-related macular degeneration
  • antioxidant
  • cerium oxide nanoparticles
  • laser-induced choroidal neovascularization
  • reactive oxygen species

Cite this

Mitra, Rajendra N. ; Gao, Ruijuan ; Zheng, Min ; Wu, Ming Jing ; Voinov, Maxim A. ; Smirnov, Alex I. ; Smirnova, Tatyana I. ; Wang, Kai ; Chavala, Sai ; Han, Zongchao. / Glycol Chitosan Engineered Autoregenerative Antioxidant Significantly Attenuates Pathological Damages in Models of Age-Related Macular Degeneration. In: ACS Nano. 2017 ; Vol. 11, No. 5. pp. 4669-4685.
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Glycol Chitosan Engineered Autoregenerative Antioxidant Significantly Attenuates Pathological Damages in Models of Age-Related Macular Degeneration. / Mitra, Rajendra N.; Gao, Ruijuan; Zheng, Min; Wu, Ming Jing; Voinov, Maxim A.; Smirnov, Alex I.; Smirnova, Tatyana I.; Wang, Kai; Chavala, Sai; Han, Zongchao.

In: ACS Nano, Vol. 11, No. 5, 23.05.2017, p. 4669-4685.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Glycol Chitosan Engineered Autoregenerative Antioxidant Significantly Attenuates Pathological Damages in Models of Age-Related Macular Degeneration

AU - Mitra, Rajendra N.

AU - Gao, Ruijuan

AU - Zheng, Min

AU - Wu, Ming Jing

AU - Voinov, Maxim A.

AU - Smirnov, Alex I.

AU - Smirnova, Tatyana I.

AU - Wang, Kai

AU - Chavala, Sai

AU - Han, Zongchao

PY - 2017/5/23

Y1 - 2017/5/23

N2 - Age-related macular degeneration (AMD) is the foremost cause of irreversible blindness in people over the age of 65 especially in developing countries. Therefore, an exploration of effective and alternative therapeutic interventions is an unmet medical need. It has been established that oxidative stress plays a key role in the pathogenesis of AMD, and hence, neutralizing oxidative stress is an effective therapeutic strategy for treatment of this serious disorder. Owing to autoregenerative properties, nanoceria has been widely used as a nonenzymatic antioxidant in the treatment of oxidative stress related disorders. Yet, its potential clinical implementation has been greatly hampered by its poor water solubility and lack of reliable tracking methodologies/processes and hence poor absorption, distribution, and targeted delivery. The water solubility and surface engineering of a drug with biocompatible motifs are fundamental to pharmaceutical products and precision medicine. Here, we report an engineered water-soluble, biocompatible, trackable nanoceria with enriched antioxidant activity to scavenge intracellular reactive oxygen species (ROS). Experimental studies with in vitro and in vivo models demonstrated that this antioxidant is autoregenerative and more active in inhibiting laser-induced choroidal neovascularization by decreasing ROS-induced pro-angiogenic vascular endothelial growth factor (VEGF) expression, cumulative oxidative damage, and recruitment of endothelial precursor cells without exhibiting any toxicity. This advanced formulation may offer a superior therapeutic effect to deal with oxidative stress induced pathogeneses, such as AMD.

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KW - reactive oxygen species

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SN - 1936-0851

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