Bioimaging is an important diagnostic tool in the investigation and visualization of biological phenomena in cells and in medicine. In this context, up-converting Gd2O3:Er3+,Yb3+ nanostructures (nanoparticles, nanorods) have been synthesized by precipitation methods and hydrothermal synthesis. Independent of size and morphology, Gd2O3:Er3+,Yb3+ powders show up-conversion (550nm, 670nm) and near-infrared emission (1.5μm) upon 980nm excitation, which makes these structures interesting for application as biomarkers. With regard to their potential application in bioimaging, cytotoxicity is an important aspect and is strongly affected by the physico-chemical properties of the investigated nanostructures. Therefore, the cytotoxic effect of bare and poly(ethylene glycol)-b-poly(acrylic acid) block co-polymer-modified nanostructures on non-phagocytic and phagocytic cells (B-cell hybridoma cells and macrophages) was investigated. The observed cytotoxic behavior in the case of macrophages incubated with bare nanostructures was assigned to the poor chemical durability of gadolinium oxide, but could be overcome by surface modification.