Fuel‐free nanomotors are essential for future in‐vivo biomedical transport and drug‐delivery applications. Herein, the first example of directed delivery of drug‐loaded magnetic polymeric particles using magnetically driven flexible nanoswimmers is described. It is demonstrated that flexible magnetic nickel–silver nanoswimmers (5–6 μm in length and 200 nm in diameter) are able to transport micrometer particles at high speeds of more than 10 μm s−1 (more than 0.2 body lengths per revolution in dimensionless speed). The fundamental mechanism of the cargo‐towing ability of these magnetic (fuel‐free) nanowire motors is modelled, and the hydrodynamic features of these cargo‐loaded motors discussed. The effect of the cargo size on swimming performance is evaluated experimentally and compared to a theoretical model, emphasizing the interplay between hydrodynamic drag forces and boundary actuation. The latter leads to an unusual increase of the propulsion speed at an intermediate particle size. Potential applications of these cargo‐towing nanoswimmers are demonstrated by using the directed delivery of drug‐loaded microparticles to HeLa cancer cells in biological media. Transport of the drug carriers through a microchannel from the pick‐up zone to the release microwell is further illustrated. It is expected that magnetically driven nanoswimmers will provide a new approach for the rapid delivery of target‐specific drug carriers to predetermined destinations.

This paper reports the fi rst proof-of-concept of using catalytic nanoshuttles to pick up, transport, and release common drug carriers including biocompatible and biodegradable polymeric particles and liposomes. The rapid transport of a wide size range of drug-loaded particles (100 nm-3.0 μ m) with a speed approximately three orders of magnitude faster than that of the particles transported by Brownian motion demonstrates the high propulsion power of the nanoshuttles. The nanoshuttles' navigation ability is illustrated by the transport of the drug carriers through a microchannel from the pick-up to the release microwell. Such ability of nanomotors to rapidly deliver drug-loaded polymeric particles and liposomes to their target destination represents a novel approach towards transporting drug carriers in a targetspecifi c manner. This also potentially addresses the obstacles of current nanoparticle drug delivery, such as off-targeting of particles. While an initial concept of actively transporting therapeutic particles is demonstrated in vitro in this paper, future efforts will focus on practical in vivo motor-based targeted drug delivery in connection to fuel-free nanovehicles. Nanoshuttles D. Kagan et al. 2742 www.small-journal.com

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Novel lipid-polymer hybrid nanoparticles are designed with a poly(ethylene glycol) coating that is shed in response to a low pH trigger. This allows the nanoparticles to be stable during systemic circulation and at neutral pH, but destabilize and fuse with lipid membranes in acidic environments. The hybrid nanoparticles consist of a poly(lactic-co-glycolic acid) core with a lipid and lipid-PEG monolayer shell. To make the hybrid nanoparticles pH sensitive, a lipid-(succinate)-mPEG conjugate is synthesized to provide a hydrolysable PEG stealth layer that is shed off the particle surface at low pH. The pH-sensitivity of the nanoparticles is tunable using the molar concentration of the lipid-(succinate)-mPEG incorporated in the lipid shell of the particles. Possible uses of these pH-sensitive nanoparticles include aggregating in the acidic tumor microenvironments, escaping the acidified endosomes, or aggregating in deep lung tissue for improved inhalation administration.