Catalase-powered nanobots are developed to overcome the mucus barrier in biological systems. The study investigates the use of these nanobots, which are propelled by hydrogen peroxide (H₂O₂), to disrupt mucus and enhance drug delivery. The nanobots are fabricated from mesoporous silica nanoparticles (MSNPs) functionalized with catalase and polyethylene glycol (PEG). They demonstrate the ability to self-propel through mucus, achieving a 60-fold increase in penetration efficiency compared to passive nanoparticles. The nanobots also disrupt the mucus layer, reducing its viscoelasticity and enabling efficient drug delivery. In vitro and ex vivo experiments confirm that the nanobots can effectively penetrate the mucus barrier, with a 65% reduction in mucus content in mouse colons. The study highlights the dual functionality of the nanobots, combining mucolytic properties and active propulsion to enhance mucus penetration. These findings suggest that catalase-powered nanobots could be promising drug delivery systems, particularly for diseases where the mucus barrier hinders therapeutic agent delivery. The results demonstrate the potential of these nanobots to improve drug delivery efficiency by penetrating the mucus barrier, which is a significant challenge in medical treatments.Catalase-powered nanobots are developed to overcome the mucus barrier in biological systems. The study investigates the use of these nanobots, which are propelled by hydrogen peroxide (H₂O₂), to disrupt mucus and enhance drug delivery. The nanobots are fabricated from mesoporous silica nanoparticles (MSNPs) functionalized with catalase and polyethylene glycol (PEG). They demonstrate the ability to self-propel through mucus, achieving a 60-fold increase in penetration efficiency compared to passive nanoparticles. The nanobots also disrupt the mucus layer, reducing its viscoelasticity and enabling efficient drug delivery. In vitro and ex vivo experiments confirm that the nanobots can effectively penetrate the mucus barrier, with a 65% reduction in mucus content in mouse colons. The study highlights the dual functionality of the nanobots, combining mucolytic properties and active propulsion to enhance mucus penetration. These findings suggest that catalase-powered nanobots could be promising drug delivery systems, particularly for diseases where the mucus barrier hinders therapeutic agent delivery. The results demonstrate the potential of these nanobots to improve drug delivery efficiency by penetrating the mucus barrier, which is a significant challenge in medical treatments.