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In addition, central nervous system neoplasm\u2010targeted nanoplatforms are urgently required. To address these issues, a new multi\u2010functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP\u2010TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione\u2010responsive disulfide bond. Mechanistically, ODP\u2010TH crosses the blood\u2013brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down\u2010regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia\u2010inducible factor\u20101\u2010<jats:italic>\u03b1<\/jats:italic> (HIF\u20101<jats:italic>\u03b1<\/jats:italic>). The results reveal that ODP\u2010TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP\u2010TH achieves a more efficient tumor\u2010inhibiting effect. This study not only overcomes the hypoxia\u2010related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi\u2010functional targeted and intensive anti\u2010tumor nanoplatform.<\/jats:p>","DOI":"10.1002\/advs.202203742","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T08:42:44Z","timestamp":1671612164000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic\u2010Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport"],"prefix":"10.1002","volume":"10","author":[{"given":"Song\u2010Yu","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Institute of Artificial Intelligence Biomedicine Engineering Research Center of Protein and Peptide Medicine Nanjing University  Nanjing 210023 P. 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