Design and applications of bispecific heterodimers: molecular imaging and beyond.

Ligand-based molecular imaging probes have been designed with high affinity and specificity for monitoring biological process and responses. Single-target recognition by traditional probes can limit their applicability for disease detection and therapy because synergistic action between disease mediators and different receptors is often involved in disease progression. Consequently, probes that can recognize multiple targets should demonstrate higher targeting efficacy and specificity than their monospecific peers. This concept has been validated by multiple bispecific heterodimer-based imaging probes that have demonstrated promising results in several animal models. This review summarizes the design strategies for bispecific peptide- and antibody-based heterodimers and their applications in molecular targeting and imaging. The design and application of bispecific heterodimer-conjugated nanomaterials are also discussed.

Influence of humic acid on titanium dioxide nanoparticle toxicity to developing zebrafish.

Titanium dioxide nanoparticle (TiO2NP) suspension stability can be altered by adsorption of dissolved organic matter (DOM). This is expected to impact their environmental fate and bioavailability. To date, the influence of DOM on the toxicity of TiO2NPs to aquatic vertebrates has not been reported. We examined the impact of Suwannee River humic acid (HA) on the toxicity of TiO2NPs to developing zebrafish (Danio rerio) in the dark and under simulated sunlight illumination. Adsorption of HA increased suspension stability and decreased TiO2NP exposure. TiO2NPs were more toxic in the presence of HA. In the absence of simulated sunlight, a small but significant increase in lethality was observed in fish exposed to TiO2NPs in the presence of HA. Under simulated sunlight illumination, photocatalytic degradation of HA reduced suspension stability. Despite the lower concentrations of Ti associated with fish in the treatments containing HA, under simulated sunlight illumination, median lethal concentrations were lower and oxidative DNA damage was elevated relative to fish exposed to TiO2NPs in the absence of HA. This study demonstrates the importance of considering environmental factors (i.e., exposure to sunlight, adsorption of DOM) when assessing the potential risks posed by engineered nanomaterials in the environment.

Titanium dioxide nanoparticles produce phototoxicity in the developing zebrafish.

Exposure of humans and other organisms to nanomaterials is increasing exponentially. It is important, but difficult, to predict the biological consequences of these exposures. We hypothesized that the unique chemical properties that make nanoparticles useful might also be the key in predicting their biological impact. To investigate this, we chose titanium dioxide nanoparticles (TiO(2)NPs) and developing zebrafish embryos as model systems. TiO(2)NPs absorb photons to generate electron-hole pairs that react with water and oxygen to form cytotoxic reactive oxygen species (ROS). Here, we show that the exposure of zebrafish embryos to TiO(2)NPs produces malformation and death, but only if the fish are also illuminated. TiO(2)NPs are taken up into the developing fish, but the egg chorion is a barrier to uptake until the embryos hatch. Chemical probes and a transgenic reporter line confirm photo-dependent production of ROS in vivo, and the addition of an ROS scavenger rescues fish embryos from toxicity. To our knowledge, this is the first study to show a photo-dependent toxic response in a whole organism from exposure to TiO(2)NPs. Of further significance, our study highlights the relationship between the property of the material that makes it useful and the biological effect that is produced. This concept should serve as a guide for future nanotoxicological studies aiming to identify potential hazardous effects on organisms.