Nomadic Nanomedicines: Medicines Enabled by the Paracrine Transfer Effect.

In nanomedicine, the cellular export of nanomaterials has been less explored than uptake. Traditionally viewed in a negative light, recent findings highlight the potential of nanomedicine export to enhance therapeutic effects. This Perspective examines key pathways for export and how nanomaterial design affects removal rates. We present the idea of the "paracrine transfer effect" (PTE), where nanomaterials are first internalized by a "waypoint" cell and then exported to a "destination" cell, influencing both in potentially exploitable ways. Essential characteristics for nanomedicines to leverage the PTE are discussed, along with two case studies: STING-stimulating polymeric nanoparticles and TLR9-stimulating liposomal spherical nucleic acids. We propose future research directions to better understand and utilize the PTE in developing more effective nanomedicines.