Cascade Catalytic Nanoparticles Selectively Alkalize Cancerous Lysosomes to Suppress Cancer Progression And Metastasis.

Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here we report an effective, selective, and safe lysosomal alkalizer that can inhibit autophagy and suppress tumors in mice. Our lysosomal alkalizer consists of an Fe x O y core that generates hydroxyl radicals (•OH) in the presence of excessive H + and H 2 O 2 inside cancer lysosomes and CeO 2-z satellites that capture and convert •OH into hydroxide ions (OH - ). Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. We show that our alkalizer effectively inhibited both local and systemic tumor growth and metastasis in mice. Our work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe. This article is protected by copyright. All rights reserved.