Genetically engineered pH-responsive silk sericin nanospheres with efficient therapeutic effect on ulcerative colitis

Xu, Sheng; Yang, Qianqian; Wang, Riyuan; Tian, Chao; Ji, Yanting; Tan, Huanhuan; Zhao, Ping; Kaplan, David L.; Wang, Feng; Xia, Qingyou

doi:10.1016/j.actbio.2022.03.012

Cited by 44 publications

(22 citation statements)

References 63 publications

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“…The effectiveness of the system was evaluated by oral delivery in an ulcerative colitis mouse model. They demonstrated improved uptake efficiency (attributed to charge interactions) and inhibition of the NF-κβ inflammatory pathway associated with acute colitis (Xu et al, 2022). Overall, the recent progress in sericin DDS highlight the advantages of the increased bioactivity and reactivity of the protein.…”

Section: Bombyx Mori Sericinmentioning

confidence: 99%

“…This means sericin materials often have increased presence of random coil structures; however, crystallinity can still be induced in the material synthesis process by techniques such as desolvation. Recent studies utilizing sericin-based DDS have focused on applications including nasal delivery (Perteghella et al, 2021), pH responsive materials (Xu et al, 2022), antibacterial activity (Baker et al, 2020;Al Masud et al, 2021), cell therapy (Orlandi et al, 2020), and cancer therapies (Boonpavanitchakul et al, 2020;Baker et al, 2021;Radu et al, 2021) (Table 1).…”

Section: Bombyx Mori Sericinmentioning

confidence: 99%

“…Perteghella et al (2021) and colleagues are working toward optimizing these particles for nose-to-brain delivery and demonstrated cytocompatibility and protection from oxidative stress in Caco-2 epithelial cells. Xu et al (2022) took a novel approach and optimized a transgenic silkworm to produce silk that is sericin-rich and has recombinant lactoferrin expressed in the sericin layer for treatment of ulcerative colitis. They were then able to synthesize ~125 nm negatively charged sericin-lactoferrin nanospheres by acetone desolvation.…”

Section: Bombyx Mori Sericinmentioning

confidence: 99%

“…One approach is to use bacteria, such as E. coli, to express silk-like peptides either alone or in combination with other useful protein sequences (Huang et al, 2015;Bowen et al, 2018;Yu et al, 2022). Another approach utilizes whole organism genetic modification to express engineered silk fibroins or other related therapeutic agents (e.g., sericins) (Xu et al, 2022;Tamura et al, 2000;Tomita et al, 2003;Xu and O'Brochta, 2015;Saviane et al, 2018;Baci et al, 2021a;Baci et al, 2021b;Zhong et al, 2011).…”

Section: Silk Fiber-inspired Recombinant Polymersmentioning

confidence: 99%

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Progress in silk and silk fiber-inspired polymeric nanomaterials for drug delivery

et al. 2022

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The fields of drug and gene delivery have been revolutionized by the discovery and characterization of polymer-based materials. Polymeric nanomaterials have emerged as a strategy for targeted delivery because of features such as their impressive biocompatibility and improved availability. Use of naturally derived polymers in these nanomaterials is advantageous due to their biodegradability and bioresorption. Natural biopolymer-based particles composed of silk fibroins and other silk fiber-inspired proteins have been the focus of research in drug delivery systems due to their simple synthesis, tunable characteristics, and ability to respond to stimuli. Several silk and silk-inspired polymers contain a high proportion of reactive side groups, allowing for functionalization and addition of targeting moieties. In this review, we discuss the main classes of silk and silk-inspired polymers that are being used in the creation of nanomaterials. We also focus on the fabrication techniques used in generating a tunable design space of silk-based polymeric nanomaterials and detail how that translates into use for drug delivery to several distinct microenvironments.

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Section: Bombyx Mori Sericinmentioning

confidence: 99%

Section: Bombyx Mori Sericinmentioning

confidence: 99%

Section: Bombyx Mori Sericinmentioning

confidence: 99%

Section: Silk Fiber-inspired Recombinant Polymersmentioning

confidence: 99%

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Progress in silk and silk fiber-inspired polymeric nanomaterials for drug delivery

et al. 2022

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“…Among various strategies for IBD treatment, two-dimensional materials (2D) with a layer structure have recently received special attention, due to the huge specific surface area and numerous reactive sites for ROS scavenging. − For example, layer montmorillonite nanosheets anchored by cerium oxide have recently exhibited an obvious anti-inflammatory efficiency for IBD treatment . On the other hand, the effective accumulation of nanoagents in damaged intestinal mucosa is highly desirable to achieve a targeted therapy with high treatment efficiency and minimal side effects. − Recently, hyaluronic acid–bilirubin nanoparticles have been reported to be accumulated in inflammatory colon epithelial cells and regulate the immune response of the inflamed colon . Hence, 2D nanoagent with excellent ROS scavenging and targeting capability is preferred and is vital for IBD treatment.…”

Section: Introductionmentioning

confidence: 99%

Ultrathin Hafnium Disulfide Atomic Crystals with ROS-Scavenging and Colon-Targeting Capabilities for Inflammatory Bowel Disease Treatment

Fan

Liu

et al. 2022

ACS Nano

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The exciting success of NBTXR3 in the clinic has triggered a tumult of activities in the design and development of hafnium-based nanoparticles. However, due to the concerns of nondegradation and limited functions, the biomedical applications of Hf-based nanoparticles mainly focus on tumors. Herein, tannic acid capped hafnium disulfide (HfS2@TA) nanosheets, a 2D atomic crystal of hafnium-based materials prepared by liquid-phase exfoliation, were explored as high-performance anti-inflammatory nanoagents for the targeted therapy of inflammatory bowel disease (IBD). Benefiting from the transformation of the S2–/S6+ valence state and huge specific surface area, the obtained HfS2@TA nanosheets were not only capable of effectively eliminating reactive oxygen species/reactive nitrogen species and downregulating pro-inflammatory factors but also could be excreted via kidney and hepatointestinal systems. Unexpectedly, HfS2@TA maintained excellent targeting capability to an inflamed colon even in the harsh digestive tract environment, mainly attributed to the electrostatic interactions between negatively charged tannic acid and positively charged inflamed epithelium. Encouragingly, upon oral or intravenous administration, HfS2@TA quickly inhibited inflammation and repaired the intestinal mucosa barrier in both dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid induced IBD models. This work demonstrated that ultrathin HfS2@TA atomic crystals with enhanced colon accumulation were promising for the targeted therapy of IBD.

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A Polysaccharide Metal Phenolic Network Nanocomposite for Theranostic Applications in Inflammatory Bowel Disease

Hu,

Wang,

Sun

et al. 2024

Adv Funct Materials

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Nanotechnology has significantly facilitated the diagnosis and therapy of inflammatory bowel disease (IBD). To obtain better therapeutic efficacy, a nanoplatform built from polysaccharides and metal‐phenolic networks (MPN) is developed here to enhance retention in the damaged intestinal region and modulate systemic immunological status in IBD models. Polysaccharides from tragacanth gum (GUM) are coordinated with iron and further interact with shikonin (Shik) to obtain a nanocomposite named Shik‐Fe@GUM. Shik‐Fe@GUM demonstrates strong and persistent accumulation in the inflamed intestinal region, which is validated in clinical specimens from IBD patients, cocultured cellular models, and living animals. Shik‐Fe@GUM served as a strong scavenger for reactive oxygen or nitrogen species in inflamed tissues or cells, and alleviated local and systemic inflammatory status by cytokine downregulation. In addition, Shik‐Fe@GUM restored the functions of damaged colonic barriers and mitigate disease activity index. The working mechanisms of Shik‐Fe@GUM are also explored and genetic sequencing results revealed that Shik‐Fe@GUM imposed its treatment effect from attenuating major inflammatory pathways. In particular, Shik‐Fe@GUM can modulate IL‐17RA relevant cell signaling and reduce the recruitment of Th17 cells (T helper cell 17). This polysaccharide‐metal‐functional molecule hybrid strategy can be broadly applicable to other IBD drugs and enhance their therapeutic index in patients.

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Genetically engineered pH-responsive silk sericin nanospheres with efficient therapeutic effect on ulcerative colitis

Cited by 44 publications

References 63 publications

Progress in silk and silk fiber-inspired polymeric nanomaterials for drug delivery

Progress in silk and silk fiber-inspired polymeric nanomaterials for drug delivery

Ultrathin Hafnium Disulfide Atomic Crystals with ROS-Scavenging and Colon-Targeting Capabilities for Inflammatory Bowel Disease Treatment

A Polysaccharide Metal Phenolic Network Nanocomposite for Theranostic Applications in Inflammatory Bowel Disease

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