Photodynamic therapy combined with oxygenating strategies are widely employed in cancer treatment, however, oxygen-boosted PDT have failed to achieve an ideal effect due to the complexity, heterogeneity, and irreversible hypoxic… Click to show full abstract
Photodynamic therapy combined with oxygenating strategies are widely employed in cancer treatment, however, oxygen-boosted PDT have 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 ROS cytotoxicity as well, such a chemodynamic approach to cancer therapy draws 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 photodynamic therapy (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 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 effects 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.
               
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