Fig. 1.

Working principle of Mito(T)-pep-Nuc(T). a Synthetic procedure of the mitochondria and nucleus dual-targeting platform, Mito(T)-pep-Nuc(T). b A schematic illustration showing the mechanism that synthesized nanomedicine could distinguish metastasis lesions from normal liver parenchyma. In cancer cells metastasized to the liver, the internalized Mito(T)-pep-Nuc(T) will be destabilized upon the cleavage mediated by the overexpressed Cathepsin B enzyme. The released MSNs and W₁₈O₄₉ NPs will then respectively target mitochondria and nucleus, consequently leading to their impairment upon laser irradiation (633 nm followed by 1064 nm in order to trigger PDT and PTT, respectively). In hepatocytes, the internalized Mito(T)-pep-Nuc(T) remains morphologically intact. Upon the irradiation with 633-nm laser, the consumption of singlet oxygen by WONPs could result in their oxidation into WO₃ featuring attenuated heating power upon subsequent laser irradiation (1064 nm). On this basis, hepatocytes and metastasis cancer cells are being treated differently, leaving only the latter one be ablated. TPP triphenyl phosphonium, WONPs W₁₈O₄₉ nanoparticles, OXPHOS oxidative phosphorylation, GLY glycolysis, PDT, photodynamic therapy, PTT photothermal therapy