Manganese/iron-based nanoprobes for photodynamic/chemotherapy combination therapy of tumor guided by multimodal imaging

Abstract

Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, but it is difficult to accurately diagnose cancer by a single imaging modality due to technical constraints. Therefore, we synthesized a type of Fe₃O₄ nanoparticle with manganese dioxide grown on the surface and then prepared it by loading photosensitive drugs and traditional Chinese medicine monomers to create an integrated diagnosis/treatment multifunctional nanoplatform: Fe₃O₄@MnO₂–celastrol (CSL)/Ce6. This nanoplatform can have full advantage of the tumor microenvironment (TME) characteristics of hypoxia (hypoxia), acidic pH (acidosis), and increased levels of reactive oxygen species (e.g., H₂O₂), even outside the TME. Specific imaging and drug release can also enhance tumor therapy by adjusting the hypoxic state of the TME to achieve the combined effect of chemotherapy (CT) and photodynamic therapy (PDT). Moreover, the obtained Fe₃O₄@MnO₂–CSL/Ce6 has H₂O₂- and pH-sensitive biodegradation and can release the anticancer drug celastrol (CSL) and photosensitizer Ce6 in TME and simultaneously generate O₂ and Mn²⁺. Therefore, the “dual response” synergistic strategy also confers specific drug release on nanomaterials, relieves tumor hypoxia and antioxidant capacity, and achieves significant optimization of CT and PDT. Furthermore, the resulting Mn²⁺ ions and Fe₃O₄ nanoparticles can be used for T₁/T₂ magnetic resonance imaging on tumor-bearing mice, and the released Ce6 can simultaneously provide fluorescence imaging functions. Therefore, Fe₃O₄@MnO₂–CSL/Ce6 realized the synergistic treatment of PDT and CT under multimodal near-infrared fluorescence/photoacoustic (photoacoustic) imaging monitoring, showing its great potential in the accurate medical treatment of tumors.