Cancer cell membrane-camouflaged nanobot assemblies augment cancer chemotherapy

Abstract

Despite rapid advancements in antitumor drug delivery, inefficient tumor penetration and compromised intracellular drug accumulation remain issues to be addressed. We report the construction of a multifunctional cancer cell membrane (CCM)-camouflaged nanobot cluster that can serve as a new generation of biomimetic motors for targeted drug delivery in cancer therapy. The resulting CCM-based nanocarriers combined the attractive properties of nanobots with the bio-interfacing properties of cell membranes. The nanocarrier, constructed by conjugating multiple Fe₃O₄ nanoparticles bearing doxorubicin hydrochloride (DOX) with CCM, demonstrated proficient operation in a biological environment. Furthermore, the nanobot displayed enhanced propulsion due to the integration of multiple Fe₃O₄ nanoparticles on the CCM. The CCM-conjugated nanobot delivered a significant amount of DOX to the nucleus of MCF-7 cells, revealing increased affinity of the particles toward cancer cells. We further investigated the release and retention of DOX from the nanobot in MCF-7 cells using an artificial intelligence (AI)-generated computer vision model. The automated method, using advanced image analysis algorithms, further indicated that intracellular DOX delivery and retention were improved with the CCM-based nanobot. In addition, the therapeutic platform showed excellent effectiveness in the ablation of MCF-7 tumor spheroids. The nanobot exhibited a stronger antitumor effect than free DOX. Our findings highlight that the CCM-conjugated nanobot, which combines the attractive properties of nanobots and cancer cell membranes, holds promise for future applications in cancer chemotherapy.