Engineering nanoparticle communication in living systems by stigmergy: An application to enhance antitumor therapy in triple-negative breast cancer

The engineering of nanoparticle communication has gained growing attention in the last years, however, efforts to communicate nanoparticles with living systems is still a barely studied emerging topic. Here, we explore a nanoparticle cooperation strategy that involves nanoparticle-cell-nanoparticle communication in vivo through stigmergy (a strategy in which nanodevices communicate by modifying the environment). First, mesoporous silica nanoparticles loaded with the senescence inductor palbociclib and coated with a heterobifunctional poly(ethylene glycol) that binds covalently to a MUC1-binding aptamer (NP(palbo)PEG-MUC1), is designed to specifically deliver the pro-senescent drug palbociclib in MDA-MB-231 breast cancer cells. Once the first nanoparticle modifies the environment due to the induction of senescence, a second community of nanoparticles, loaded with the senolytic navitoclax and coated with a hexa-oligo-saccharide (NP(nav)-Gal), releases its cargo to eliminate tumor senescent cells selectively. The targeted therapy through stigmergy communication is tested in vitro, and in vivo, where delays tumor growth and reduces metastases in a mouse model of human triple-negative breast cancer while minimizing undesired drugs side effects.