MnS Nanocapsule Mediates Mitochondrial Membrane Permeability Transition for Tumor Ion-Interference Therapy

"Structure subserves function" is one fundamentalbiological maxim, and so the biological membrane that delimits theregions primarily serves as the margin between life and death forindividual cells. Here, an Oswald ripening mechanism-guided solvothermalmethod was proposed for the synthesis of uniform MnS nanocapsulesassembled with metastable & gamma;-MnS nanocrystals. Through designingthe physicochemical properties, MnS nanocapsules would disaggregateinto small & gamma;-MnS nanocrystals in a tumor acidic environment,with the surface potential switched from negative to positive, thusshowing conspicuous delivery performance. More significantly, thespecific accumulation of Mn2+ in mitochondria was promoteddue to the downregulation of mitochondrial calcium uptake 1 (MICU1)by the formed H2S, thus leading to serious mitochondrialMn-poisoning for membrane permeability increase and then tumor apoptosis.This study provides a synthesis strategy of metal sulfide nanocapsulesand encourages multidisciplinary researchers to focus on ion-cancercrosstalk for the development of an antitumor strategy.