Accumulation of inorganic nanostructures in the excretory system organs increases their likelihood of toxicity and interference with common medical diagnoses. Thus, one of the major concerns regarding their clinical translation is related to their persistence in organisms. Here the authors demonstrate that nano-architectures composed by hollow silica nanocapsules embedding arrays of ultrasmall gold nanoparticles undergo biodegradation in cellular environment affording small, potentially clearable building blocks. Furthermore, the authors present their exploitation in glutathione-triggered release of covalently loaded cisplatin prodrug. This endogenously triggered release leads to high cytotoxicity to human pancreatic carcinoma cells, setting the way for promising applications to synergistic dual chemo/radio-therapy and radio-imaging.