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The success of nanoparticle-based cancer therapies ultimately depends on their ability to selectively and efficiently accumulate in regions of disease. Outfitting nanoparticles to actively target tumor-specific markers has improved specificity, yet it remains a challenge to amass adequate therapy in a selective manner. To help address this challenge, we have developed a mechanism of nanoparticle amplification based on stigmergic (environment-modifying) signalling, in which a “Signalling” population of gold nanorods induces localized unveiling of cryptic collagen epitopes, which are in turn targeted by “Responding” nanoparticles bearing gelatin-binding fibronectin fragments. We demonstrate that this two-particle system results in significantly increased, selective recruitment of responding particles. Such amplification strategies have the potential to overcome limitations associated with single-particle targeting by leveraging the capacity of nanoparticles to interact with their environment to create abundant new binding motifs., National Institutes of Health (U.S.). Bioengineering Research Partnership (R01CA124427-01), National Institutes of Health (U.S.) (National Cancer Institute (U.S.) U54CA119349), National Institutes of Health (U.S.) (National Cancer Institute (U.S.) U54CA119335), National Institutes of Health (U.S.) (National Cancer Institute (U.S.) Alliance Challenge Project/MIT-Harvard Center of Cancer Nanotechnology Excellence U54CA151884), David & Lucile Packard Foundation (Fellowship 1999-1453), Marie D. and Pierre Casimir-Lambert Fund, National Institute of General Medical Sciences (U.S.) (Medical Scientist Training Program T32GM007753), Whitaker Foundation, National Science Foundation (U.S.)