Photodynamic therapy (
PDT) combined with oxygenating strategies is widely employed in
cancer treatment; however,
oxygen-boosted
PDT has failed to achieve an ideal effect due to the complexity, heterogeneity, and irreversible hypoxic environment generated by
tumor tissues. With the emergence of Fe-dependent ferroptosis boasting
reactive oxygen species (ROS) cytotoxicity as well, such a chemodynamic approach to
cancer therapy has drawn extensive attention. In this study,
hemoglobin (Hb) is connected with the
photosensitizer chlorin e6 (Ce6) to construct a 2-in-1 nanoplatform (SRF@Hb-Ce6) with
Sorafenib (SRF, ferroptosis promotor) loaded, combining
oxygen-boosted
PDT and potent ferroptosis. Benefiting from the intrinsic presence of Fe capable of binding
oxygen,
hemoglobin concurrently furnishes
oxygen for
oxygen-dependent
PDT and Fe for Fe-dependent ferroptosis. Furthermore, amphiphilic MMP2-responsive
peptide is incorporated into the skeleton of the nanoplatform to ensure drug-release specificity for safety improvement. Correlative measurements demonstrate the potentiation of
PDT and ferroptosis with SRF@Hb-Ce6. More importantly,
PDT strengthens ferroptosis by recruiting immune cells to secrete IFN-γ, which can sensitize the
tumor to ferroptosis in our findings. The
therapeutic effect of synergistic treatment with SRF@Hb-Ce6 in vitro and in vivo was proven significant, revealing the promising prospects of combined
PDT and ferroptosis
therapy with the 2-in-1 nanoplatform.