Macrophage-Membrane-Coated Enzyme-Driven Nanorobot for Tumor Organoids Penetration and Cancer Treatment

The development and application of drug delivery systems based on micro/nanorobots have been a hot research field in recent years. Due to the complexity of living organisms, micro/nanorobots need to overcome a series of physiological obstacles. The development of micro/nanorobot drug delivery systems capable of targeted navigation to locate tumor sites, achieving self-sustained propulsion, deep penetration of tumor sites, and controllable drug release, remains challenging. Here, we designed a macrophage membrane-coated enzyme-driven pH-responsive nanorobot UDM-M1Mo̷M-pHRL(DOX). The M1 macrophage membrane (M1Mo̷M) provides active tumor targeting for nanorobots, the urease-driven motor (UDM) provides endogenous power for nanorobots, and pH-responsive drug carriers (pHRL(DOX)) provide tumor tissue-controlled drug release effects for nanorobots. Therefore, this nanorobot combines the ability of directional navigation of tumor sites, self-sustaining propulsion, effective penetration of tumor tissues, and controllable drug release. This nanorobot has significant tissue penetration and antitumor effects on human-derived tumor organoids constructed in vitro. After entering the bloodstream, nanorobots can move quickly and target tumors, achieve effective drug enrichment in tumor tissues, and exhibit excellent antitumor therapeutic effects. The materials used in this nanorobot are mostly endogenous and have high biological safety, providing a reference significance for the clinical treatment of cancers.