Nanozyme-functionalized microalgal biohybrid microrobots in inflammatory bowel disease treatment

Abstract

Oral drugs are the most direct and effective strategy for the treatment of gastrointestinal diseases. However, the harsh environment of gastric juice, lack of targeted lesion sites, and rapid metabolism present difficulties in the development of oral drugs. This research introduces a nanozyme-functionalized microalgal biohybrid microrobot (Hp@CS-PNAs@PAA) with a novel mechanism for treating inflammatory bowel disease (IBD) by leveraging the therapeutic advantages of microalgae and nanozymes. The microrobot uniquely combines the natural antioxidant capacity of Hematococcus pluvialis (Hp) microalgae and the catalytically active enzyme-mimicking properties of platinum-based nanoparticle assemblies (PNAs), enabling enhanced scavenging of reactive oxygen species (ROS) and targeted anti-inflammatory effects. Through its layered design, the Hp@CS-PNAs@PAA microrobot can navigate the gastrointestinal tract, resist degradation, and target inflamed colon tissues via electrostatic interactions, achieving extended retention and prolonged therapeutic action at inflammation sites. This study demonstrated that the synergistic anti-inflammatory effects of the microrobot derive from its ability to reduce ROS, inhibit proinflammatory cytokines, and promote the expression of tight junction proteins critical for preserving the integrity of the intestinal barrier. Both in vitro and in vivo tests in a DSS-induced colitis mouse model revealed that this system effectively restores damaged tissues by reducing oxidative stress and inflammation, indicating significant potential for clinical application in the management of colitis and similar inflammatory diseases.