Transition metal‐based nanoparticles have shown their broad applications in versatile biomedical applications. Although traditional iron‐based nanoparticles have been extensively explored in biomedicine, transition metal manganese (Mn)‐based nanoparticulate systems have emerged as a multifunctional nanoplatform with their intrinsic physiochemical property and biological effect for satisfying the strict biomedical requirements. This comprehensive review focuses on recent progress of Mn‐based functional nanoplatforms in biomedicine with the particular discussion on their elaborate construction, physiochemical property, and theranostic applicability. Several Mn‐based nanosystems are discussed in detail, including solid/hollow MnO_x nanoparticles, 2D MnO_x nanosheets, MnO_x‐silica/mesoporous silica nanoparticles, MnO_x‐Fe₃O₄ nanoparticles, MnO_x‐Au, MnO_x‐fluorescent nanoparticles, Mn‐based organic composite nanosystem, and some specific/unique Mn‐based nanocomposites. Their versatile biomedical applications include pH/reducing‐responsive T₁‐weighted positive magnetic resonance imaging, controlled drug loading/delivery/release, protection of neurological disorder, photothermal hyperthermia, photodynamic therapy, chemodynamic therapy, alleviation of tumor hypoxia, immunotherapy, and some specific synergistic therapies, which are based on their disintegration behavior under the mildly acidic/reducing condition, multiple enzyme‐mimicking activity, catalytic‐triggering Fenton reaction, etc. The biological effects and biocompatibility of these Mn‐based nanosystems are also discussed, accompanied with a discussion on challenges/critical issues and an outlook on the future developments and clinical‐translation potentials of these intriguing Mn‐based functional nanoplatforms.

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