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.