Wednesday, February 3, 2021

Mesopore to Macropore Transformation of Metal–Organic Framework for Drug Delivery in Inflammatory Bowel Disease

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Mesopore to Macropore Transformation of Metal–Organic Framework for Drug Delivery in Inflammatory Bowel Disease

A mechanism for inflammation‐targeting drug delivery by Ce‐MOF@PSS is proposed. Negatively charged Ce‐MOF@PSS nanoparticles selectively adhere to inflamed tissue. Reactive oxygen species produced by activated immune cells at the inflamed mucosa induces transformation of Ce‐MOF@PSS from mesoporous to macroporous and local drug release. Specific drug delivery exhibits superior therapeutic effect over free drug administration.


Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease that is characterized by segmental intestinal inflammation. There is an urgent need for more efficient inflammation‐targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation‐responsive metal–organic framework material (Ce‐MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema. The overproduced reactive oxygen species (ROS) at inflammatory sites induces transformation of Ce‐MOF@PSS from mesopore to macropore with local drug release. In experimental colitis, the Ce‐MOF@PSS delivery system exhibits excellent inflammation‐targeting efficacy and superior therapeutic effect over free drug on suppressing inflammation and repairing intestinal barrier function. Accordingly, by targeting intestinal inflammation, increasing local drug concentrations, scavenging ROS, reducing systemic exposure, and exhibiting excellent safety profi les, it is considered that the Ce‐MOF drug delivery platform can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.

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