Engineering Crystallinity Gradients for Tailored CaO2 Nanostructures: Enabling Alkalinity-Reinforced Anticancer Activity with Minimized Ca2+/H2O2 Production

CaO2 nanoparticles (CNPs) can produce toxic Ca2+ and H2O2 under acidic pH, which accounts for their intrinsic anticancer activity but at the same time raises safety concerns upon systemic exposure. Simultaneously realizing minimized Ca2+/H2O2 production and enhanced anticancer activity poses a dilemma. Herein, we introduce a crystallinity gradient-based selective etching (CGSE) strategy, which is realized by creating a crystallinity gradient in a CNP formed by self-assembled nanocrystals. The nanocrystals distributed in the outer layer have a higher crystallinity and thus are chemically more robust than those distributed in the inner layer, which can be selectively etched. CGSE not only leads to CNPs with tailored single- and double-shell hollow structures and metal-doped compositions but more surprisingly enables significantly enhanced anticancer activity as well as tumor growth inhibition under limited Ca2+/H2O2 production, which is attributed to an alkalinity-reinforced lysosome-dependent cell death pathway.

Automated summary

The study introduces a crystallinity gradient-based selective etching strategy to control the structure and composition of CaO2 nanoparticles. This strategy not only reduces the production of harmful substances and enhances anticancer activity, but also inhibits tumor growth through the lysosome-dependent cell death pathway.