Fe-doped mesoporous silica catalyzes ascorbic acid oxidation for tumor-specific therapy in scaffold

Ascorbic acid (AA) is a promising antitumor agent, yet its autooxidation is too slow which constrains the further application. Fortunately, the autoxidation process can be accelerated by transition metal catalysts, especially Fe³⁺ ions. In this study, AA was loaded to Fe-doped mesoporous silica (designated as AA@Fe-SiO₂), which was introduced into poly-L-lactic acid (PLLA) and then prepared into a scaffold. Mechanistically, AA@Fe-SiO₂ degraded in acidic tumor microenvironment because excessive H⁺ substituted Fe atoms in the iron silicate framework, releasing Fe³⁺ and AA. The Fe³⁺ boosted the pro-oxidation reaction of AA, generating numerous hydrogen peroxide (H₂O₂) and Fe²⁺. Then, Fe²⁺ reacted with H₂O₂ to initiate Fenton reactions favoring hydroxyl radical generation, triggering oxidative damage on tumor cells to implement tumor-specific therapy. Results showed that the release amount of AA in acidic solution was about 3 times higher than that in neutral solution, which was attributed to the pH-dependency of the degradation of AA@Fe-SiO₂ in scaffold. Furthermore, the scaffold generated numerous ascorbate radical intermediate and increased the H₂O₂ concentration by 120.2%, demonstrating that Fe³⁺ remarkably accelerated the oxidation rate of AA. Cell experimental results showed that the scaffold caused massive apoptosis of tumor cells, while no obvious cytotoxicity to normal cells, confirming the antitumor specificity of scaffold. This work paves a promising way to construct a biodegradable and catalytic scaffold, featuring effective tumor-specific therapy.