Enzyme-instructed morphology transformation of mitochondria-targeting peptide for the selective eradication of osteosarcoma.

The treatment of osteosarcoma involves an adjuvant therapy that combines surgery and chemotherapy. However, considering that children are the main victims of osteosarcoma, replacing such a harsh treatment with a soft but powerful method that ensures a complete cure while having no adverse effects is highly desirable. To achieve this aim, we have developed a supramolecular therapeutic strategy based on morphology-transformable mitochondria-targeting peptides for the eradication of osteosarcoma with enhanced selectivity and reduced side effects. A newly designed micelle-forming amphiphilic peptide, l-Mito-FFYp, consisting of a phosphate substrate for the biomarker enzyme of osteosarcoma alkaline phosphatase (ALP), disassembles in response to the ALP enzyme in the cell membrane to generate positively charged l-Mito-FFY molecules, which diffuse inside the targeted cell and self-assemble to form nanostructures specifically inside the mitochondria to induce cell apoptosis.