The infinitesimal machine surgeon: prospects for upconversion nanoparticles driving molecular motors/nanomachines

The concept of the “infinitesimal machine surgeon” was envisaged by Feynman in 1959 and 1983, describing a miniature, human-controllable machine capable of being directed to biological tissue to perform a physical intervention. This perspective explores the potential of combining Feringa-type rotary molecular motors (nanomachines) with upconversion nanoparticles (UCNPs) to realise the vision of the infinitesimal machine surgeon. In this approach, UCNPs convert near-infrared (NIR) excitation into ultraviolet/visible (UV/Vis) emission to activate molecular nanomachines within biological tissue. The fundamental operating principles are outlined, recent experimental advances in powering molecular motors and UCNPs in organic solvents are reviewed. Simple biophotonic calculations based on the Beer–Lambert law suggest that upconversion from 808 nm to 450–475 nm may offer a promising excitation strategy for activating molecular motors in biological tissues. Key challenges to biological implementation are identified, including permissible tissue light-exposure levels and the effects of tissue absorption and multiple scattering on the photon budget available to drive UCNPs and molecular motors. Finally, experimental strategies for evaluating these systems in biologically relevant environments are proposed, in accordance with the 3Rs principles of biomedical research.