A H₂O₂ self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy

Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H₂O₂) into toxic hydroxyl radicals (˙OH) to kill cancer cells, holds high promise in tumor therapy due to its high selectivity. However, the anticancer efficacy is unsatisfactory owing to the limited concentration of endogenous H₂O₂. Herein, thermal responsive nanoparticles with H₂O₂ self-sufficiency are fabricated by utilizing organic phase change materials (PCMs) to encapsulate iron-gallic acid nanoparticles (Fe-GA) and ultra-small CaO₂. PCMs, acting as the gatekeeper, could be melted down by the hyperthermia effect of Fe-GA under laser irradiation with a burst release of Fe-GA and CaO₂. The acidic tumor microenvironment would further trigger CaO₂ to generate a large amount of H₂O₂ and Ca²⁺. The self-supplied H₂O₂ would be converted into ˙OH by participating in the Fenton reaction with Fe-GA. Meanwhile, in situ generation of Ca²⁺ could cause mitochondrial damage and lead to apoptosis of tumor cells. With efficient tumor accumulation illustrated in in vivo photoacoustic imaging, Fe-GA/CaO₂@PCM demonstrated a superior in vivo tumor-suppressive effect without inducing systemic toxicity. The study presents a unique domino effect approach of PCM based nanoparticles with thermal responsiveness, H₂O₂ self-supply, and greatly enhanced CDT effects, showing bright prospects for highly efficient tumor treatment.