Nanoparticle self-assembly gated by logical proteolytic triggers

The emergent electromagnetic properties of nanoparticle self-assemblies are being harnessed to build new medical and biochemical assays with unprecedented sensitivity. While current self-assembly assays have displayed superior sensitivity for single molecular targets, the development of systems with the capacity to process multiple inputs may more effectively decipher complex disease signatures such as cancer. Herein, we present the design and synthesis of nanoparticles that perform Boolean logic operations using two proteolytic inputs associated with unique aspects of tumorigenesis (MMP2 and MMP7). Using dynamic light scatting, fluorescence, and MRI, we show that logical AND and OR functions can control the self-assembly of disperse superparamagnetic nanoparticles and enable remote, NMR detection of nanoparticle computation. In the future, by increasing the complexity of assembly triggers, nanoparticles may be tailored to sense a diversity of disease inputs in vitro and potentially in vivo.