In 2021, Science posed a century-defining question for nanomedicine: Will injectable, disease-fighting nanobots ever be a reality? Recently, Guan's group from Wuhan University of Technology (China) provided a compelling answer by reporting an injectable nanorobot for precision cancer therapy. This study, entitled "Bienzyme-powered nanorobots with ultrasensitive chemotaxis for precision cancer therapy" was published in National Science Review and offers direct and affirmative evidence addressing the question raised by Science.
Inspired by automobiles combining an engine and a steering wheel, they reported nanorobots integrating two kinds of enzymes with distinct functionalities to control propulsion and orientation. Specifically, they integrated catalase and urease onto the same hemispheres of Au nanoparticles to develop Janus nanorobots. Urease works for propulsion by harnessing endogenous urea in bloodstream and tumor microenvironments, while catalase controls orientation by sensing the H2O2 concentration gradient typically existing in tumor microenvironments. With the synergistic effects of these two enzymatic reaction systems, propulsion and orientation are decoupled in nanorobots, offering significantly enhanced chemotactic sensitivity toward tumor-specific biomarkers H2O2.
After intravenous administration into a tumor-bearing mouse model, these nanorobots achieved high targeting efficiency, deep penetration, and significant cell internalization. Compared with the passively diffused counterparts, their tumor-targeting efficiency, penetration depth, and cell internalization were improved 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 propulsion-enhanced chemotaxis strategy reported in this work is broadly applicable for diverse chemotactic nanorobot systems by tailoring the combinations of chemical reaction systems. In the future, the same strategy could be extended to the treatment of inflammation, infection, and other diseases characterized by localized biochemical gradients.
To promote clinical translation, Guan's group has established a company dedicated to advancing injectable nanorobots toward medical applications. With continued optimization, rigorous evaluation, and interdisciplinary collaboration, the researchers anticipate that injectable nanorobots can move from experimental models to clinical practice in the foreseeable future, offering new hope for patients facing cancer and other challenging diseases.
