Bienzyme-powered nanorobots with ultrasensitive chemotaxis for precision cancer therapy

Abstract Low tumor-targeting delivery efficiency (Ɛ) and poor tumor penetration remain critical issues in the clinical translation of nanoparticle-based drug delivery systems. Here we report that bienzyme-powered Janus nanorobots with catalase and urease covering the same hemispheres in sequence demonstrate chemical propulsion far exceeding translational Brownian forces and torques comparable to rotational Brownian torques by leveraging endogenous urea and H₂O₂ gradient in tumor microenvironment, showcasing ultrasensitive chemotaxis toward biomarkers over-expressed by tumor tissues centimeters away and augmented Ɛ. After intravenous injection into a tumor-bearing mouse model, the nanorobots demonstrate significant enhancement in Ɛ, penetration depth, and cell internalization, surpassing those of passive counterparts by 209, >10, and 1970 times, respectively. When loaded with antitumor drugs, they boost the tumor suppression efficacy by approximately 49 times compared with the passive counterparts. This work offers a new strategy for the next-generation drug delivery, promising a paradigm shift for self-propelled nanorobots in precision medicine.