Tyrosinase-Woven Melanin Nets for Melanoma Therapy through Targeted Mitochondrial Tethering and Enhanced Photothermal Treatment.

Abstract

Manipulating intracellular biological processes and organelles has emerged as a pivotal strategy to influence cellular physiological functions. Mitochondria, recognized as the powerhouse of cells, play a crucial role in tumorigenesis and progression. Inspired by the Nature's tyrosinase-catalyzed melanin formation within melanoma cells, here an approach is developed using a polysaccharide dually-functionalized with tyrosine and triphenylphosphine (TPP) for targeted mitochondria cross-linking in melanoma cells. This technique intricately weaves melanin nets within the cells, serving as a tether for the mitochondria and effectively decelerating tumor metabolism through nanoparticle-net transformation. Tyrosinase acts as the "needle", while the functionalized polysaccharide serves as the "string" successfully constructing nets within the cell. Furthermore, the tyrosinase-catalyzed cross-linking of tyrosine not only facilitates the production of artificial melanin but also enhances the photothermal conversion efficiency of melanoma cells, leading to decrease of the tumor growth. This study unveils a non-drug method for regulating organelle physiological activity and introduces photothermal treatment. This work not only sheds light on the manipulation of cellular functions but also holds promise for advancing cancer therapeutic strategies.