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Inflammatory targeted nanoplatform incorporated with antioxidative nano iron oxide to attenuate ulcerative colitis
Haojun Chen1, Wei Sun2, Can Li3
1Co-Innovation Center for Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.
Abstract:
Antioxidative nanomaterials with reactive oxygen species (ROS) scavenging capabilities hold promise for the treatment of ulcerative colitis (UC). However, their clinical application is limited by rapid diffusion, susceptibility to inactivation, and insufficient targeting of inflammatory sites. This study focuses on developing a nanoplatform by integrating iron oxide nanoparticles (IONPs) into zeolitic imidazolate frameworks-8 (ZIF-8), termed as ZIF-8@IONPs. ZIF-8@IONPs exhibited good biocompatibility and effective ROS scavenging capabilities in RAW 264.7 cells. To enhance inflammatory targeting, HA@ZIF-8@IONPs were generated through hyaluronic acid (HA) surface modification. HA@ZIF-8@IONPs effectively reduced damage to intestinal tissues in the UC mouse model. Mechanistic revealed that HA@ZIF-8@IONPs exhibited antioxidant and anti-inflammatory activities by eliminating endogenous ROS, activating the Nrf2 signaling pathway, and inhibiting the NF-κB signaling pathway. This study highlights the nanoplatform's potential as a promising candidate for UC treatment due to its great targeting of inflammatory microenvironments and efficient ROS scavenging.
Insights
This study developed HA@ZIF-8@IONPs, a novel nanoplatform for ulcerative colitis (UC) treatment. The nanoplatform effectively targets inflammation and scavenges reactive oxygen species (ROS), showing promise for UC therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gastroenterology
Background:
- Antioxidative nanomaterials offer potential for ulcerative colitis (UC) treatment by scavenging reactive oxygen species (ROS).
- Clinical use of current nanomaterials is hindered by poor targeting, diffusion, and inactivation.
- Novel nanoplatforms are needed to improve efficacy and targeting in inflammatory bowel disease.
Purpose of the Study:
- To develop and evaluate a novel nanoplatform, ZIF-8@IONPs, for enhanced ROS scavenging and targeting in UC.
- To improve the targeting efficiency of ZIF-8@IONPs through hyaluronic acid (HA) surface modification.
- To investigate the therapeutic potential of HA@ZIF-8@IONPs in a UC mouse model.
Main Methods:
- Integration of iron oxide nanoparticles (IONPs) into zeolitic imidazolate frameworks-8 (ZIF-8) to create ZIF-8@IONPs.
- Surface modification of ZIF-8@IONPs with hyaluronic acid (HA) to form HA@ZIF-8@IONPs for enhanced targeting.
- In vitro evaluation of ROS scavenging and biocompatibility in RAW 264.7 cells.
- In vivo assessment of HA@ZIF-8@IONPs in a mouse model of ulcerative colitis.
Main Results:
- ZIF-8@IONPs demonstrated good biocompatibility and effective ROS scavenging.
- HA@ZIF-8@IONPs exhibited enhanced targeting of inflammatory sites.
- Treatment with HA@ZIF-8@IONPs significantly reduced intestinal tissue damage in the UC mouse model.
- Mechanistic studies revealed ROS elimination, Nrf2 pathway activation, and NF-κB pathway inhibition by HA@ZIF-8@IONPs.
Conclusions:
- HA@ZIF-8@IONPs represent a promising nanoplatform for ulcerative colitis therapy.
- The nanoplatform's efficacy stems from targeted delivery to inflammatory microenvironments and potent ROS scavenging.
- This study provides a foundation for developing advanced nanomedicines for inflammatory bowel diseases.
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