The use of nanoparticles holds promising new applications in medicine. Among the nanoparticles, Solid lipid nanoparticles (SLN) are noteworthy because they are produced with biodegradable and biocompatible components. Several studies have shown that cells can internalize and process SLN, and much has been studied about their therapeutic effects. Surprisingly, little research has investigated how SLN affect intracellular signaling pathways. The study of endocytosis associated with signaling is indispensable to understand the impact of these nanoparticles on eukaryotic cells. Previous results from our laboratory showed a correlation between SLN internalization and galectin-8 translocation into the nucleus of prostate cancer cells (PC-3). Galectin-8 is related to the activation of the TGF-β signaling pathway. This pathway is deregulated in advanced stages of cancer, increasing cell migration and invasion. Here, we evaluate the effects of SLN on the TGF-β signaling pathway. Uncovering the underlying mechanisms that may be triggered by nanoparticles in cancer cells may be helpful to develop and make use of safer nanomedicine tools.