Petunidin-Capped Zinc Oxide Nanoparticles Inhibit Migration, Invasion, and Epithelial-Mesenchymal Transition in Renal Cell Carcinoma via Transcription Factor EB-Mediated Autophagy Activation

Abstract

Context: Renal cell carcinoma (RCC) is a common malignancy characterised by high recurrence rates and resistance to available therapies. Objective: This study investigates the anti-tumour potential of petunidin-capped zinc oxide nanoparticles (PTN-ZnONPs), synthesised through a green reduction approach using zinc acetate as the precursor. Petunidin (PTN) was selected due to its well-documented anticancer properties. Method: Physicochemical characterisation confirmed successful nanoparticle formation, with a UV–visible absorption peak at 359 nanometers. Although the primary crystallite size was 20.51 nanometers, morphological analysis revealed the formation of stable aggregates with an average size of approximately 100 nanometers. Results: In vitro experiments demonstrated that PTN-ZnONPs significantly inhibited RCC cell migration and invasion. Western blotting and immunofluorescence analyses showed that treatment reversed epithelial–mesenchymal transition by increasing E-cadherin expression and reducing N-cadherin and vimentin levels. In addition, PTN-ZnONPs activated autophagic flux, as evidenced by elevated ATG5 and ATG12 expression, an increased LC3-II to LC3-I ratio, and enhanced nuclear translocation of transcription factor EB (TFEB). Mechanistic studies involving TFEB knockdown markedly reduced these inhibitory effects, confirming that the TFEB-mediated autophagic pathway is the principal driver of the anti-metastatic activity of PTN-ZnONPs. Conclusions: Collectively, these findings indicate that PTN-ZnONPs represent a promising therapeutic strategy for RCC by suppressing tumour progression through coordinated regulation of autophagy and epithelial–mesenchymal transition.