Targetable Mesoporous Silica Nanoprobes for Mapping the Subcellular Distribution of H2Se in Cancer Cells

Hydrogen selenide, a highly active reductant, is believed as a key molecule in the cytotoxicity of inorganic selenium compounds. However, the detail mechanism has hardly been studied because the distribution of H2Se in the subcellular organelles remains unclear. Herein, we exploited a series of novel targetable mesoporous silica nanoplatforms to map the distribution of H2Se in cytoplasm, lysosome, and mitochondria of cancer cells. The subcellular targeting moiety-conjugated mesoporous silica nanoparticles were assembled with a near-infrared fluorescent probe (NIR-H2Se) for detecting endogenous H2Se in the corresponding organelles. The confocal fluorescence imaging of cancer cells induced by Na2SeO3 found out a higher concentration of H2Se accumulated only in mitochondria. Consequently, the H2Se burst in mitochondria-triggered mitochondrial collapse that led to cell apoptosis. Hence, the selenite-induced cytotoxicity in cancer cells associates with the alteration in mitochondrial function caused by high level of H2Se. These findings provide a new way to explore the tumor cell apoptosis signaling pathways induced by Na2SeO3, meanwhile, we propose a research strategy for tracking the biomolecules in the subcellular organelles and the correlative cellular function and related disease diagnosis.