Biomineralized synthesis of a smart O₂-regenerating nanoreactor for highly efficient starvation/gas therapy

The emerging starvation therapy holds great promise in cancer treatment, however, its therapeutic effect is heavily reduced by intracellular hypoxia and high glutathione (GSH) conditions. To overcome these limitations, a new concept of starvation therapy pattern that employs biodegradable carriers with special selectivity and exhibits excellent anti-migration and therapy effect without using any invasive chemotherapy drugs was developed. A facile biomineralization method is first chosen to synthesize human serum albumin and folic acid modified MnO₂ to guarantee active targeting, long-term stability and responsive degradation in tumor microenvironment. Designed degradation remarkably reduces GSH contents and hugely elevates intracellular O₂ levels, both of which significantly improve the catalytic efficiency of GOX. Furthermore, the by-product of H₂O₂ is intelligently used to oxidize L-arginine and the generated NO results into effective gas therapy. More importantly, the first anti-migration case of starvation therapy has been reported in this work, and detailed molecular mechanism study uncovers that lysosome damage and changes of mitochondria membrane potential contribute to cell apoptosis. This work opens up new ideas to construct novel green yet noninvasive methods to treat cancer and inhibit migration by using degradable carriers and endogenous substances to minimize adverse effect.