Oxyhemoglobin nano-recruiter preparation and its application in biomimetic red blood cells to relieve tumor hypoxia and enhance photodynamic therapy activity

Abstract

Photodynamic therapy (PDT) is strongly O₂ dependent. Therefore, its therapeutic effects are seriously hindered in hypoxic tumors. Red blood cells are responsible for delivering O₂ in the blood. In this manuscript, biomimetic red blood cells (BRBCs) were exploited using a layer-by-layer assembly method, using Fe₃O₄@CuO, oxyhemoglobin (OxyHb), a photosensitizer and a photo-cross linked acrylate modified hyaluronic acid (HA) gel shell. The Fe₃O₄@CuO core has very high OxyHb loading efficiency (the adsorption capacity of Fe₃O₄@CuO for OxyHb is derived to be 0.99 mg mg⁻¹) to ensure a sufficient O₂ supply. OxyHb was protected well by the HA shell in order to avoid O₂ release during the delivery process in blood before arrival at the tumor tissue. The HA shell protection can be eliminated in position at the tumor to trigger O₂ release through hyaluronidase (HAase) triggered HA degradation. Furthermore, Fe₃O₄ in the nanosystem can provide magnetic field assisted tumor targeting and magnetic resonance imaging of the tumor. Therefore, this work presents a highly efficient all-in-one biomimetic nanomedicine approach to overcome hypoxia and achieve tumor targeting theranostics.