1. Enhanced Ferroptosis by Oxygen-Boosted Phototherapy Based on a 2-in-1 Nanoplatform of Ferrous Hemoglobin for Tumor Synergistic Therapy
- Author
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Siwen Li, Yueqing Gu, Zhiyu Qian, Huixin Hu, Qinling Yuan, Tian Xu, Janiqua Rolle, Xinkai Hu, and Yuying Ma
- Subjects
Sorafenib ,Cell Survival ,medicine.medical_treatment ,General Physics and Astronomy ,chemistry.chemical_element ,Photodynamic therapy ,Antineoplastic Agents ,Breast Neoplasms ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Oxygen ,Hemoglobins ,Mice ,In vivo ,medicine ,Animals ,Ferroptosis ,Humans ,General Materials Science ,Photosensitizer ,Cytotoxicity ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,Mice, Inbred BALB C ,Photosensitizing Agents ,Dose-Response Relationship, Drug ,General Engineering ,021001 nanoscience & nanotechnology ,eye diseases ,0104 chemical sciences ,chemistry ,Photochemotherapy ,Cancer research ,Nanoparticles ,Female ,0210 nano-technology ,medicine.drug - Abstract
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.
- Published
- 2020