Light/gas cascade-propelled Janus micromotors that actively overcome sequential and multi-staged biological barriers for precise drug delivery

Abstract Passive diffusion-based drug delivery systems have indeed shown impressive performance to overcome a cascade of biological barriers, but the delivery efficiency is still modest. Although artificial micro/nanomotors are capable of autonomous movement, oriented navigation and seeking target actively represent an alternative and attractive strategy to revolutionize drug delivery patterns potentially, the separated and single propulsion mode of motors still hampers their further biomedical application that needs to overcome successive biological barriers. Herein, we demonstrated a cascaded NIR-light/gas-driven Janus calcium carbonate particle micromotors (JCPMs) to overcome multi-staged biological barriers and achieved active drug delivery. These JCPMs exhibited NIR light-driven thermophoretic motion with precisely steered start/stop switch, speed, and motion trajectory in biological media and displayed CO2-bubbles-powered autonomous propulsion in an acidic environment. With the collaborative use of cascaded light/gas double-mode driving, JCPMs displayed a multistage self-adapted strategy to overcome sequential biological barriers during tumor-targeted drug delivery in a cascaded manner, involving of light-driven active tumor cells seeking, facilitated tumor penetration and cellular membranes traversal by virtue of photo-thermomechanical force and self-thermophoretic propulsion, gas-driven lysosomes escape and intracellular drug release successively. Such a strategy guaranteed trajectory-controllable active drug delivery to exert the selective tumor therapeutic effect as well as avoided side effects. We envisioned that the proposed cascaded driving mode of micromotors for traversing biological barriers would boost the delivery efficiency for tumor treatment, which may pave a convenient and versatile way to develop next generation active vehicles in the biomedical field.