Targeted Magnetic Resonance Imaging and Modulation of Hypoxia with Multifunctional Hyaluronic Acid‐MnO₂ Nanoparticles in Glioma

Abstract

Manganese dioxide (MnO 2 )-based nanoparticles are a promising tumor microenvironment-responsive nanotheranostic carrier for targeted magnetic resonance imaging (MRI) and for alleviating tumor hypoxia. However, the complexity and potential toxicity of the present common synthesis methods limit their clinical application. Herein, multifunctional hyaluronic acid-MnO 2 nanoparticles (HA-MnO 2 NPs) are synthesized in a simple way by directly mixing sodium permanganate with HA aqueous solutions, which serve as both a reducing agent and a surface-coating material. The obtained HA-MnO 2 NPs show an improved water-dispersibility, fine colloidal stability, low toxicity, and responsiveness to the tumor microenvironment (high H 2 O 2 and high glutathione, low pH). After intravenous injection, HA-MnO 2 NPs exhibit a high imaging sensitivity for detecting rat intracranial glioma with MRI for a prolonged period of up to 3 d. These nanoparticles also effectively alleviate the tumor hypoxia in a rat model of intracranial glioma. The downregulation of VEGF and HIF-1α expression in intracranial glioma validates the sustained attenuation effect of HA-MnO 2 NPs on tumor hypoxia. These results show that HA-MnO 2 NPs can be used for sensitive, targeted MRI detection of gliomas and simultaneous attenuation of tumor hypoxia. Cancer TheranosticsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

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“…Manganese oxides, which decompose to release paramagnetic Mn ions triggered by tumor-microenvironment (weakly acidic, excessive H 2 O 2, and GSH), are explored for glioma imaging. Generally, Mn oxides are formed on the biocompatible macromolecules that act as the growing template, such as poly(allylamine hydrochloride) (PAH) [ 44 ], hyaluronic acid (HA) [ 45 ], human or bovine serum albumin (HSA/BSA) [ 46 – 48 ] and transferrin (Tf) [ 49 ] through a redox reaction or biomineralization process. Fu et al synthesized HA-MnO 2 nanoparticles through directly mixing NaMnO 4 with HA aqueous solution wherein HA served as both reductant and template for MnO 2 growth [ 45 ].…”

Gold-based Inorganic Nanohybrids for Nanomedicine Applications

“…In addition, MnO 2 nanomaterials can respond to tumor microenvironment cues such as hypoxia, acidosis, and vascular endothelial growth factor, which can be utilized to amplify their diagnostic and therapeutic performance. For example, MnO 2 nanosheets will rapidly decompose and release Mn 2+ under mildly acidic and reducing conditions, thus enhancing the contrast of T 1 MR imaging 153 , 153 . Moreover, the released Mn 2+ could initiate Fenton chemistry to kill cancer cells by catalyzing tumor endogenous H 2 O 2 into toxic reactive oxygen species 149 .…”

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