The complex nature of tissue-deteriorating diseases, particularly those with inflammatory components such as arthritis, underscores the demand for precision medicine targeting specific sites. Charged biocompatible polymeric nanoparticles (NPs) have had wide applicability as efficient delivery vehicles, capitalizing on electrostatic interactions for enhanced uptake into charged tissue such as cartilage. However, the efficiency of these delivery systems relies on their interactions with the local microenvironment of the targeted tissue, which may be significantly altered in pathological conditions.