Biomineralized Bimetallic Oxide Nanotheranostics for Multimodal Imaging-Guided Combination Therapy

The hypoxia of the tumor microenvironment (TME) often hinders the effectiveness of cancer treatments, especially O(2)-dependent photodynamic therapy (PDT). Methods: An integrated iridium oxide (IrO(2))-manganese dioxide (MnO(2)) nanotheranostic agent was fabricated through bovine serum albumin (BSA)-based biomineralization of Ir(3+) and Mn(2+). BSA was first covalently modified with chlorin e6 (Ce6), and used to fabricate multifunctional BSA-Ce6@IrO(2)/MnO(2) nanoparticles (NPs) for computed X-ray tomography (CT) and photoacoustic (PA) imaging-guided PDT and photothermal (PTT) therapy of cancer. Extensive in vitro and in vivo studies were performed. Results: The theranostic agent produced can relieve tumor hypoxia by the decomposition of endogenous H(2)O(2) in cancer cells to oxygen. The oxygen generated can be exploited for improved PDT. Paramagnetic Mn(2+) released from the NPs in the acidic TME permits magnetic resonance imaging (MRI) to be performed. The exceptional photothermal conversion efficiency (65.3%) and high X-ray absorption coefficient of IrO(2) further endow the NPs with the ability to be used in computed CT and PA imaging. Extensive antitumor studies demonstrated that the BSA-Ce6@IrO(2)/MnO(2) nanoplatform inhibits cancer cell growth, particularly after combined PTT and PDT. Systematic in vivo biosafety evaluations confirmed the high biocompatibility of the nanoplatform. Conclusion: This work not only provides a novel strategy for designing albumin-based nanohybrids for theranostic applications but also provides a facile approach for extending the biomedical applications of iridium-based materials.