These findings promote the optimization of nanovehicles for transport of drugs through the BBB. The insulin coating of the particles enabled targeting of specific brain regions, suggesting the potential use of INS-GNPs for delivery of various treatments for brain-related disorders.

Exosomes have many biological functions as short‐ and long distance nanocarriers for cell‐to‐cell communication. They allow the exchange of complex information between cells, and thereby modulate various processes such as homeostasis, immune response and angiogenesis, in both physiological and pathological conditions. In addition, due to their unique abilities of migration, targeting, and selective internalization into specific cells, they are promising delivery vectors. As such, they provide a potentially new field in diagnostics and treatment, and may serve as an alternative to cell‐based therapeutic approaches. However, a major drawback for translating exosome treatment to the clinic is that current understanding of these endogenous vesicles is insufficient, especially in regards to their in vivo behavior. Tracking exosomes in vivo can provide important knowledge regarding their biodistribution, migration abilities, toxicity, biological role, communication capabilities, and mechanism of action. Therefore, the development of efficient, sensitive and biocompatible exosome labeling and imaging techniques is highly desired. Recent studies have developed different methods for exosome labeling and imaging, which have allowed for in vivo investigation of their bio‐distribution, physiological functions, migration, and targeting mechanisms. These improved imaging capabilities are expected to greatly advance exosome‐based nanomedicine applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Biological logic gates are smart probes able to respond to biological conditions in behaviors similar to computer logic gates, and they pose a promising challenge for modern medicine. Researchers are creating many kinds of smart nanostructures that can respond to various biological parameters such as pH, ion presence, and enzyme activity. Each of these conditions alone might be interesting in a biological sense, but their interactions are what define specific disease conditions. Researchers over the past few decades have developed a plethora of stimuli‐responsive nanodevices, from activatable fluorescent probes to DNA origami nanomachines, many explicitly defining logic operations. Whereas many smart configurations have been explored, in this review we focus on logic operations actuated through fluorescent signals. We discuss the applicability of fluorescence as a means of logic gate implementation, and consider the use of both fluorescence intensity as well as fluorescence lifetime.

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.

• CAD requirements can be based on lung cancer screening trial results. • CAD systems can be evaluated using publically available annotated CT image databases. • A new CAD system was developed with a low false positive rate. • The CAD system has reliable measurement tools needed for clinical use.