A superoxide dismutase/catalase mimetic nanomedicine for targeted therapy of inflammatory bowel disease

Zhang, Qixiong; Tao, Hui; Lin, Yongyao; Ying, Hanjie; An, Huijie; Zhang, Dinglin; Feng, Shibin; Hu, Houyuan; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

doi:10.1016/j.biomaterials.2016.08.010

Cited by 186 publications

(146 citation statements)

References 60 publications

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“…[35] At 4 h after oral delivery, ex vivo imaging showed significantly higher fluorescent signals in colons from colitis mice compared to those of healthy mice ( Figure 3A, the left panel). [31,36] We then evaluated the colonic accumulation of Cy7.5-AON in mice with DSS-induced colitis after oral administration. This was also affirmed by quantification of the Ac2-26 content in the colonic tissues by HPLC ( Figure S7A, Supporting Information).…”

Section: The Distribution Of Orally Delivered Aon In the Inflamed Colonmentioning

confidence: 99%

“…[26][27][28] While currently developed NPs are able to protect the loaded biologic drugs from hydrolysis in the gut, low bioavailability is generally observed due to insufficient and uncontrolled release at diseased sites, thereby leading to undesirable efficacies. Based on our existing expertise in ROS-responsive nanovehicles and the potency of Ac2-26, [30][31][32][33][34] we developed an Ac2-26 peptidecontaining nanotherapy for site-specific delivery to the inflamed colon in IBD. [26] As well documented, oxidative stress, characterized by overproduced reactive oxygen species (ROS), is closely related to the pathogenesis of IBD.…”

Section: Introductionmentioning

confidence: 99%

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A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

et al. 2019

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The incidence and prevalence of inflammatory bowel disease (IBD) increases steadily worldwide. There is an urgent need for effective and safe IBD therapies. Accelerated resolution of inflammation is a new strategy for the management of inflammatory diseases. For effective and safe IBD treatment, herein a smart nanotherapy (i.e. oxidation‐responsive nanoparticles containing a proresolving annexin A1‐mimetic peptide Ac2‐26, defined as AON) is developed, which can release packaged Ac2‐26, in response to highly expressed reactive oxygen species (ROS) at diseased sites. AON effectively protects Ac2‐26 from degradation in the enzyme‐rich environment of the gastrointestinal tract. By delivering this nanotherapy to the inflamed colons of mice with IBD, site‐specific release and accumulation of Ac2‐26 in response to high levels of ROS at the inflammatory sites are achieved. Mechanistically, the Ac2‐26‐containing, oxidation‐labile nanotherapy AON effectively decreases the expression of proinflammatory mediators, attenuates trafficking and infiltration of inflammatory cells, promotes efferocytosis of apoptotic neutrophils, and increases phenotypic switching of macrophages. Therapeutically, AON reduces symptoms of inflammation, accelerates intestinal mucosal wound healing, reshapes the gut microbiota composition, and increases short‐chain fatty acid production. Additionally, oral delivery of this nanomedicine shows excellent safety profile in a mouse model, conferring the confidence for further development of a targeted precision therapy for IBD and other inflammatory diseases.

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Section: The Distribution Of Orally Delivered Aon In the Inflamed Colonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

et al. 2019

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“…Likewise, administration of a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger (Tempol) suppresses the expression of pro-inflammatory mediators in different mouse models of colitis [79]. In rats, treatment with different doses of SOD attenuates colonic tissue damages and lipid peroxidation in a dose dependent manner and reduces rolling and adhesion of leukocytes in venules [80].…”

Section: Role Of Neutrophil-derived Moleculesmentioning

confidence: 99%

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Wéra

Lancellotti

Oury

2016

JCM

230

189

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Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn’s disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD.

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“…ROS are involved in the progression of aging as well as neurodegenerative diseases, vascular and cancer diseases, and diabetes [2]. Reactive oxygen species (ROS) take part in different chemical reactions with proteins, leading to fragmented and cross-linked proteins [3].…”

Section: Introductionmentioning

confidence: 99%

“…SOD is considered as the first line of defense against oxidative stress. The enzyme has antiaging, antiviral, and anti-inflammatory effects [1,2,6]. SOD has been widely applied in the cosmetics, pharmaceutical, and food industries [6].…”

Section: Introductionmentioning

confidence: 99%

Co-Immobilization of Superoxide Dismutase with Catalase on Soft Microparticles Formed by Self-Assembly of Amphiphilic Poly(Aspartic Acid)

Mao

Wang

et al. 2017

Catalysts

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Through genetic engineering technology, catalase (CAT) and superoxide dismutase (SOD) have been separately fused to an elastin-like polypeptide (ELP). Thus, the enzymes can be purified through phase transition. Hexadecylamine-modified poly(aspartic acid) (HPASP) is able to self-assemble, forming soft microparticles. The HPASP microparticles were used to co-immobilize SOD-ELP and CAT-ELP through amidation reaction. Circular dichroism (CD) confirmed that the secondary structures of the co-immobilized enzymes have been preserved. Fluorescence spectra showed that the co-immobilized enzymes exhibited a higher stability than the free enzymes. Dismutation of superoxide by superoxide dismutase (SOD) generates hydrogen peroxide. By using the co-immobilized enzymes (SOD-ELP/CAT-ELP@HPASP), the generated hydrogen peroxide of SOD-ELP can be decomposed in situ by CAT-ELP. Activity assay results demonstrated that the superoxide anion (•O 2 − ) scavenging ability is 63.15 ± 0.75% for SOD-ELP/CAT-ELP@HPASP.The advantages of the approach of enzyme co-immobilization include the fact that the soft support HPASP itself is a polypeptide in nature, the stability of immobilized enzymes is improved, and a high activity has been achieved. Potentially SOD-ELP/CAT-ELP@HPASP can be applied in the cosmetic industry.

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A superoxide dismutase/catalase mimetic nanomedicine for targeted therapy of inflammatory bowel disease

Cited by 186 publications

References 60 publications

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Co-Immobilization of Superoxide Dismutase with Catalase on Soft Microparticles Formed by Self-Assembly of Amphiphilic Poly(Aspartic Acid)

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