Nanorobotic Approaches Against Multidrug-Resistant Infections: Design, Principle, Mechanistic Innovation, Translational Challenges and Biomedical Applications

The efficacy of traditional antimicrobial treatments has been largely compromised due to the high occurrence of multidrug-resistant (MDR) pathogens, therefore underlining the limitations of existing drug delivery mechanisms. Pathogens resist pharmacological treatment via different mechanisms, including efflux pump overexpression, biofilm formation, and enzymatic destruction. The application of nanorobotics or controllable nanoscale devices has gained considerable attention for overcoming shortcomings while connecting biomedical engineering, materials science, and microbiology. Despite advancements in nanomedicine, there is still no suitable nanorobotic system applicable against MDR pathogens. Previous studies highlighted device categories and materials but did not explain the detailed nanorobotic mobility, sensing, and programmability to counteract biological resistance. This review combines cross-disciplinary discoveries to design a mechanistic and translational model for nanorobotics effective in controlling infectious diseases while focusing on the advancements in nanorobotic technologies over the past six years (2020–2025), with emphasis on translational readiness, biosafety issues, scalability, regulation, and their mechanistic ability to overwhelm MDR complications. Databases from different publishers, including PubMed, Scopus, and Web of Science, were used to select studies focusing on the potential of emerging nanorobotic therapeutic technologies, such as magnetic microrobots, catalytic nanoswimmers, and DNA origami nanodevices, and their application to bacterial biofilms and antibiotic drug delivery. Evidence from the literature shows that magnetically driven microrobots, catalytic nanoswimmers, and DNA origami structures can actively destroy biofilms, enhance antibiotic penetration, and perform site-specific antimicrobial administration. Nevertheless, most of these innovations remain in the preclinical or prototype stage, hindered by biosafety issues, immunological reactivity, poor routing precision, energy source optimization, and a lack of regulatory and ethical frameworks, which are major challenges for clinical translation.