Y Gd F :Yb/Er mesocrystals with a biocompatible surface and diverse morphological characteristics were successfully synthesized using chitosan-assisted solvothermal processing. Their structural properties, studied using X-ray powder diffraction, Fourier transform infrared spectroscopy, scanning and transmission electron microscopy and energy dispersive X-ray analysis, were further correlated with the up-conversion emission (λ = 976 nm) recorded in function of temperature. Based on the change in the visible green emissions originating from the thermally coupled H and S levels of Er , the corresponding LIR was acquired in the physiologically relevant range of temperatures (25-50 °C). The detected absolute sensitivity of about 0.0042 °C , along with the low cytotoxicity toward both normal human lung fibroblasts (MRC-5) and cancerous lung epithelial (A549) cells, indicate a potential for use in temperature sensing in biomedicine. Additionally, their enhanced internalization in cells, without suppression of cell viability, enabled in vitro labeling of cancer and healthy cells upon 976 nm laser irradiation.