Microrobotic copper-rich electrochemical interfacing for targeted cancer theranostics in the gut

Abstract

The exquisite spatiotemporal regulation of drug biodistribution is paramount for optimal targeted cancer theranostics. Robotic ingestible devices promise to reinvent the way drugs interact with gastrointestinal (GI) tissues and malignant tumors. However, no study has yet demonstrated theranostic functions beyond merely conveying synthetic drugs. Here, we present an orally administrable, functionally integrated soft microrobot capable of localized therapeutic regulation of copper (Cu)-dependent cell death mechanism, termed "cuproptosis" within GI tumors. By leveraging the interplay of mechanical, electrical, and biochemical functions, the robot actively targets and grasps the tumor and generates anticancer Cu-rich electrochemical interfacing with the targeted tumor microenvironment. This tumor-robot interface, characterized by in situ generated electric multipole fields and on-demand burst Cu2+ ion release, induces similar to 10(4)-fold increase in local concentration of Cu2+ ions, and drives their dense accumulation and directed infiltration for effective cuproptotic cancer treatment, with tumor penetration capabilities far beyond those of passive diffusion. Demonstrations of minimally invasive, long-range tumor targeting in porcine organs and mouse tumor eradication in vivo demonstrate the translational potential of our approach as microrobotic theranostic platforms for targeting GI cancer.