Current medicine could greatly improve by intelligent treatment systems able to respond autonomously to early stages of diseases from within a patient. As an initial study en route to such a system, we describe biologically relevant logic gates based on gold nanoparticles (GNPs) and fluorescent molecules that are able to respond to multiple input parameters so as to detect specific biological conditions all through the lens of fluorescence lifetime (FLT) imaging microscopy (FLIM). By conjugating the pH-responsive Oregon Green 488 (OG) to the GNPs by a trypsin-cleavable peptide, we manufactured GNP–OG constructs, which are responsive to two separate inputs: surrounding pH and proteinase presence. The GNP–OG constructs can sensitively detect and distinguish between conditions of low pH and no enzyme, the presence of one of either raised pH or enzyme, and the presence of both. Additionally, the GNP–OG probes were tested on ex vivo mouse organs to demonstrate further biological relevance and successfully behaved as various logic gates would be expected in different organs where pH and enzyme conditions vary. Altogether, the GNP–OG constructs are shown to carry out logic gate behaviors, where the desired gate is defined by the FLT detected. Unlike previous biological logic gates, the GNP–OG constructs can realize AND, OR, NAND, NOR, XOR, and XNOR gates by choosing different FLT cutoffs alone. The constructs make for efficient fluorescent logic detectors independent of concentration and so can serve as a stepping stone toward more complex logic systems.

Surgical blades are common medical tools. However, blades cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage, lengthening recovery, and increasing pain. We propose that surgical procedures can rely on natural tissue remodeling tools-enzymes, which are the same tools our body uses to repair itself. Through a combination of nanotechnology and a controllably activated proteolytic enzyme, we performed a targeted surgical task in the oral cavity. More specifically, we engineered nanoparticles that contain collagenase in a deactivated form. Once placed at the surgical site, collagenase was released at a therapeutic concentration and activated by calcium, its biological cofactor that is naturally present in the tissue. Enhanced periodontal remodeling was recorded due to enzymatic cleavage of the supracrestal collagen fibers that connect the teeth to the underlying bone. When positioned in their new orientation, natural tissue repair mechanisms supported soft and hard tissue recovery and reduced tooth relapse. Through the combination of nanotechnology and proteolytic enzymes, localized surgical procedures can now be less invasive.

Nearly 20% of cultured shrimp die every year due to viral diseases. In this study, we evaluated the capacity of nanoparticulate RNA interference (RNAi) to down-regulate genes in Penaeus vannamei shrimp and protect shrimp against white spot syndrome virus (WSSV, i.e. white spot disease).