Theranostics 2020; 10(2):841-855. doi:10.7150/thno.40715

Research Paper

Biomineralized Bimetallic Oxide Nanotheranostics for Multimodal Imaging-Guided Combination Therapy

Jianrong Wu1, Gareth R. Williams2, Shiwei Niu1, Yanbo Yang1, Yu Li1, Xuejing Zhang1, Li-Min Zhu1✉

1. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P.R. China
2. UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK

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Citation:
Wu J, Williams GR, Niu S, Yang Y, Li Y, Zhang X, Zhu LM. Biomineralized Bimetallic Oxide Nanotheranostics for Multimodal Imaging-Guided Combination Therapy. Theranostics 2020; 10(2):841-855. doi:10.7150/thno.40715. Available from https://www.thno.org/v10p0841.htm

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Abstract

The hypoxia of the tumor microenvironment (TME) often hinders the effectiveness of cancer treatments, especially O2-dependent photodynamic therapy (PDT).

Methods: An integrated iridium oxide (IrO2)-manganese dioxide (MnO2) nanotheranostic agent was fabricated through bovine serum albumin (BSA)-based biomineralization of Ir3+ and Mn2+. BSA was first covalently modified with chlorin e6 (Ce6), and used to fabricate multifunctional BSA-Ce6@IrO2/MnO2 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 H2O2 in cancer cells to oxygen. The oxygen generated can be exploited for improved PDT. Paramagnetic Mn2+ 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 IrO2 further endow the NPs with the ability to be used in computed CT and PA imaging. Extensive antitumor studies demonstrated that the BSA-Ce6@IrO2/MnO2 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.

Keywords: iridium oxide/manganese dioxide, multimodal imaging, photothermal/photodynamic therapy, biomineralization, nanomedicine