Polymer dynamic organic theranostic spheres (PolyDOTS) are being studied as a photothermal ablation treatment of cancer and are activated by blue or near-infrared light. PolyDOTS or related hybrid polymeric nanoparticle products could be mass-produced, and it is expected that they, like any other engineered nanoparticle (ENP), could be found in aquatic environments. The purpose of this study was to investigate the potential toxicity of these types of hybrid nanoparticles on nontarget marine organisms. To investigate the potential of even greater toxicity due to solar exposure, the PolyDOTS were exposed to the sun for 12 h and "charged". Once charged, hepatopancreas and gill tissues from oysters (Crassostrea virginica) were exposed to concentrations of both uncharged and charged PolyDOTS for 24 h in vitro. The effects of PolyDOTS on lysosomal destabilization, cell viability, and free radical damage were analyzed. Significant sublethal toxicity was observed with the charged particles, and reduced viability was observed with uncharged particles in vitro. In vivo imaging studies using IVIS (In Vivo Imaging System) indicated PolyDOTS uptake in tissues. These types of studies are important for understanding the potential effects of light sensitive ENPs in oysters and their broader ecological impacts on estuarine ecosystems.