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

Abstract

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 an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (center dot OH) in the presence of excessive H+ and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert center dot OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe. A cascade catalytic nanoparticle with high biocompatibility is reported, serving as a potent lysosomal alkalizer capable of converting excessive hydrogen peroxide and H+ into hydroxide ions only in cancerous lysosomes, leading to lysosomal alkalization and consequent suppression of tumor progression and metastasis.image