Biocompatible Reactive Oxygen Species (ROS)‐Responsive Nanoparticles as Superior Drug Delivery Vehicles

Zhang, Dinglin; Wei, Yanling; Chen, Kai; Zhang, Xiangjun; Xu, Xiaoqiu; Shi, Qi; Han, Songling; Chen, Xin; Gong, Hao; Li, Xiaohui; Zhang, Jianxiang

doi:10.1002/adhm.201400299

Cited by 121 publications

(95 citation statements)

References 38 publications

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“…This was mainly resulted from hydrolysis of Ac2-26 in the harsh environment of the gastrointestinal tract, which is a major challenge for oral delivery of peptides/proteins. [30,32] More importantly, our comprehensive in vitro and in vivo studies have revealed good safety profile for nanocarriers based on OxbCD. Our previous studies substantiated that NPs based on a ROS-responsive material OxbCD can be selectively hydrolyzed under inflammatory conditions with overexpressed ROS, while they are stable in the stomach.…”

Section: Discussionmentioning

confidence: 94%

“…[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: Discussionmentioning

confidence: 94%

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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“…370 ROS species such as hydroxyl radicals (HO • ) and hydrogen peroxide (H 2 O 2 ) are produced in different parts of the cell as a by-product of electron transfer reactions. 370 In one study well-defined ROS-sensitive β-CD-based smart DDSs 371 were prepared by incorporation of oxidation-responsive boronic ester units into the structure. Cytocompatible micelles containing polypropylene sulfide (PPS) were developed to form a ROS-triggered drug release system taking advantage of the increased hydrophilicity of the PPS core that was disassembled after oxidation by the ROS rich environment.…”

Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

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New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

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“…ROS are known to be elevated during ischemia and to remain elevated during the first 24 h post reperfusion, the period which represents the most relevant and effective clinical time point for treatment of MI. [19] Furthermore, the unique ROS-responsive nanoparticles described here could be utilized for in vivo molecular imaging of ROS levels in order to diagnose ischemic conditions or to validate anti-oxidative treatment strategies following I/R injury. Thus, a ROS-responsive nanoparticle drug-delivery system offers a promising approach for the treatment of various I/R injuries such as stroke and renal infarction.…”

mentioning

confidence: 99%

“…[13] Increased production of ROS occurs in ischemia/reperfusion independent of the organ involved. [19] Currently, ROS levels are generally measured and monitored either in vitro using isolated cardiac myocytes or ex vivo using a Langendorff perfused heart. Furthermore, ROS generation has been described in several pathological processes such as cancer, diabetes, and aging, as well as inflammation-mediated diseases such as rheumatoid arthritis.…”

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confidence: 99%

A Self‐Assembled Fluorescent Nanoprobe for Imaging and Therapy of Cardiac Ischemia/Reperfusion Injury

Ziegler

Yap

et al. 2019

Advanced Therapeutics

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There is a strong medical need for precision imaging of ischemic tissue and even more so for delivery of drugs specifically to the ischemic tissue at risk of functional damage. To date, no targeting epitopes or mechanisms have been established in ischemia/reperfusion injury that allow specific molecular targeting for either diagnosis or therapy, a deficiency that contributes to myocardial infarction being the leading cause of mortality and a major contributor to morbidity worldwide. Reactive oxygen species (ROS) are locally increased at the site of ischemia/reperfusion injury. Utilizing these as a unique molecular targeting mechanism in developing ROS-responsive nanoparticles, this study illustrates unique designed ROS-responsive, self-assembled fluorescent nanoparticles as tools for diagnostic and therapeutic targeting of tissue that is undergoing ischemia/reperfusion injury. This ROS-responsive fluorescent nanoprobe has been evaluated in a mouse model of myocardial infarction, applying 1 h of ischemia via temporary ligation of the left anterior descending coronary artery and measuring fluorescence signals after reperfusion. This study shows highly specific targeting to the ischemic/reperfused myocardium throughout the first 24 h post reperfusion. Overall, this study identifies ROS-responsive fluorescent nanoparticles as an ideal platform for the localized delivery of imaging agents and novel therapeutics to the infarcted myocardium.Myocardial infarction (MI) is the leading single cause of death and a major contributor to morbidity worldwide. [1] MI is usually caused by the rupture of atherosclerotic plaques, leading to

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Biocompatible Reactive Oxygen Species (ROS)‐Responsive Nanoparticles as Superior Drug Delivery Vehicles

Cited by 121 publications

References 38 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

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

A Self‐Assembled Fluorescent Nanoprobe for Imaging and Therapy of Cardiac Ischemia/Reperfusion Injury

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