Nutrient-Delivery and Metabolism Reactivation Therapy for Melanoma

To fulfil the demands of rapid proliferation, tumour cells, including those in melanoma, undergo significant metabolic alterations, with some pathways being upregulated while others are downregulated. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of inversely downregulated metabolic pathways has therapeutic effects remains unexplored. Here, we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. Briefly, L-tyrosine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impedes the proliferation of melanoma cells, primaryly through the inhibition of glycolysis. We discovered that reduced glycolysis was a consequence of pyruvate kinase activity inhibition by melanin intermediates indole-5,6-quinone. Furthermore, leaveraging melanin as a natural photothermal reagent for photothermal therapy (PTT), we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and PTT. To the best of our knowledge, this is the first study of metabolism activation-based tumour treatment, suggesting specific nutrients as potent activators of metabolic pathways.