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

Li, Chenwen; Yang, Zhao; Cheng, Juan; Guo, Jian; Zhang, Qixiong; Zhang, Xiangjun; Ren, Jiandong; Wang, Fengchao; Huang, Jun; Hu, Houyuan; Wang, Ruibing; Zhang, Jianxiang

doi:10.1002/advs.201900610

Cited by 131 publications

(102 citation statements)

References 72 publications

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“…For instance, by taking advantages of the elevated ROS level in ulcerative colon 8 , the ROS-responsive nanoparticles (NPs) based on β-cyclodextrin derivatives firstly developed by Zhang and Li et al exhibited an excellent safety profile, improved drug accumulation in the inflammatory colon, and enhanced the therapeutic efficacy against UC 9 . With the same ROS-responsive nanomedicine platform, pro-resolving peptide Ac2-26 was released in the high ROS environment specifically in the UC colon, driving inflammatory resolution effectively 10 . In spite of these significant progresses, many challenges still exist with these novel nanomedicines, such as low accumulation in the colon tissues, fast clearance, and little distinction in actions on different cell types.…”

Section: Introductionmentioning

confidence: 99%

Amelioration of ulcerative colitis via inflammatory regulation by macrophage-biomimetic nanomedicine

et al. 2020

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Ulcerative colitis (UC) is featured with relapsing inflammation in the colon, where macrophages are recruited and polarized locally into M1 type to drive further inflammation. Pharmacotherapy of UC has exhibited limited efficacy, mostly due to the poor specificity. Methods: A macrophage-biomimetic nanomedicine was developed for targeted treatment of UC, which was derived from reactive oxygen species (ROS)-sensitive β-cyclodextrin, loaded with rosiglitazone, and coated with macrophage membrane. The ability of the nanomedicine in regulating macrophage polarization was examined at cellular level, and the macrophage-tropism driven targeted delivery into the inflammatory colon was investigated by ex vivo bio-imaging distribution assay. Furthermore, the nanomedicine's therapeutic efficacy was systemically examined in dextran sulfate sodium (DSS)-induced colitis model in mice. Results: The nanomedicine effectively polarized macrophages to M2 and protected epithelial cells from oxidative stress in vitro . In addition, macrophage-membrane led the nanomedicine to the inflammatory colon with a high targeting efficiency. In response to the elevated ROS in the inflammatory tissue, the nanomedicine released rosiglitazone specifically and regulated macrophage polarization in vivo . Macrophage membrane also assisted inflammation suppression by sequestering proinflammatory cytokines. Working in such a synergy, the nanomedicine exhibited significant therapeutic effects against UC in mice. Conclusions: This macrophage-biomimetic nanomedicine leverages the inflammatory tropism and inflammatory cytokine sequestration effects of macrophage membrane for targeted delivery and local inflammation suppression, the ROS-responsiveness of β-cyclodextrin-based matrix for specific payload release, and the macrophage-polarizing effect of rosiglitazone for inflammatory regulation, thereby exhibiting considerable therapeutic efficacy against UC in mice. This study offers important new insights on the design and development of biomimetic nanomaterials for inflammation regulations.

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Section: Introductionmentioning

confidence: 99%

Amelioration of ulcerative colitis via inflammatory regulation by macrophage-biomimetic nanomedicine

et al. 2020

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“…Dextran sulfate sodium salt (DSS) disrupts the mucosal barrier of the colon, causing intestinal inflammation, weight loss, and other clinical symptoms, thus becoming a common agent for clinically induced colitis 40 . C57/BL6 mice in the experimental group were orally treated with DSS ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Upconversion optogenetic micro-nanosystem optically controls the secretion of light-responsive bacteria for systemic immunity regulation

et al. 2020

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Chemical molecules specifically secreted into the blood and targeted tissues by intestinal microbiota can effectively affect the associated functions of the intestine especially immunity, representing a new strategy for immune-related diseases. However, proper ways of regulating the secretion metabolism of specific strains still remain to be established. In this article, an upconversion optogenetic micro-nanosystem was constructed to effectively regulate the specific secretion of engineered bacteria. The system included two major modules: (i) Modification of secretory light-responsive engineered bacteria. (ii) Optical sensing mediated by upconversion optogenetic micro-nanosystem. This system could regulate the efficient secretion of immune factors by engineered bacteria through optical manipulation. Inflammatory bowel disease and subcutaneously transplanted tumors were selected to verify the effectiveness of the system. Our results showed that the endogenous factor TGF-β1 could be controllably secreted to suppress the intestinal inflammatory response. Additionally, regulatory secretion of IFN-γ was promoted to slow the progression of B16F10 tumor.

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“…More recently, our studies showed that OxbCD nanoparticles are able to package a proresolving annexin A1-mimetic peptide Ac2-26, offering a ROS-responsive peptide nanotherapy (defined as AON) ( Fig. 6 A-E) [ 321 ]. AON effectively protected Ac2-26 from degradation in the gastrointestinal environment ( Fig.…”

Section: Treatment Of Inflammatory Diseases By Bioresponsive Drug Delmentioning

confidence: 99%

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

Ding

et al. 2020

Journal of Controlled Release

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Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted.

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

Cited by 131 publications

References 72 publications

Amelioration of ulcerative colitis via inflammatory regulation by macrophage-biomimetic nanomedicine

Amelioration of ulcerative colitis via inflammatory regulation by macrophage-biomimetic nanomedicine

Upconversion optogenetic micro-nanosystem optically controls the secretion of light-responsive bacteria for systemic immunity regulation

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

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