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Unfortunately, there are no effective measures to prevent or inhibit this disease. In this study, biodegradable Mn<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> nanoparticles (NPs) in different shapes are prepared and enclosed them by {100}, {200} and {103} facets that exhibit facet\u2010dependent protection against neurotoxicity induced by oxidative damage in a cell model of PD. Notably, Mn<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> nanorods enclosed by {103} facets exhibit high levels of enzyme\u2010like activity to eliminate reactive oxygen specie in vitro. It is also determined that the uptake pathway of Mn<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> NPs into MN9D cells is mediated by caveolin. The data demonstrate that Mn<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> nanorods can be taken up by cells effectively and confer excellent levels of neuroprotection while the biodegradation of Mn<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> NPs in vivo is confirmed by photoacoustic image of Mn<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> NPs in brain at 60 d. 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