Abnormal metabolic symbiosis is a typical characteristic
that differentiates
the tumor regions from healthy tissues and meanwhile maintains tumor
survival. It is of great potential to disrupt intratumoral metabolic
symbiosis in tumor therapy. Herein, we report a specific tumor therapy
strategy through inducing acidosis to disrupt intratumoral metabolic
symbiosis for tumor elimination, which is based on carbonic anhydrase
inhibitor (CAI)-modified ferrous sulfide nanoparticles (FeS-PEG-CAI
NPs). The FeS-PEG-CAI NPs show the acid-responsive degradation capacity
to release functional components, including CAI, Fe2+,
and H2S, while remaining quite stable under normal physiological
conditions. The generated CAI and H2S gas can not only
disrupt the intracellular metabolic symbiosis to induce acidosis but
also provide suitable circumstances for Fe2+-mediated Fenton
reaction, producing abundant toxic hydroxyl radicals. Meanwhile, these
NPs also show the dual-mode imaging capacity with photoacoustic and
magnetic resonance imaging, which can dynamically monitor tumor location
in the process of synergistic chemodynamic/photothermal/gas therapy.
Overall, the developed FeS-PEG-CAI NPs exert their role of disrupting
intratumoral metabolic symbiosis and other synergistic effects, which
further enrich tumor treatment strategies.