Efficient signal amplification processes are key to the design of sensitive assays for biomolecule detection. Here, we describe a new assay platform that takes advantage of both polymerization reactions and the aggregation of nanoparticles to amplify signal. In our design, a cascade is set up in which radicals generated by either enzymes or metal ions are polymerized to form polymers that can entangle multiple gold nanoparticles (AuNPs) into aggregates, resulting in a visible color change. Less than 0.05% monomer-to-polymer conversion is required to initiate aggregation, providing high sensitivity toward the radical generating species. Good sensitivity of this assay toward horseradish peroxidase, catalase, and parts per billion concentrations of iron and copper is shown. Incorporation of the oxygen-consuming enzyme glucose oxidase (GOx), enables this assay to be performed in open air conditions at ambient temperature. We anticipate that such a design will provide a useful platform for sensitive detection of a broad range of biomolecules through polymerization-based amplification.