Phase‐Dependent Antitumor Activity of Manganese Sulfide Nanomaterials

Crystal polymorph engineering represents a pivotal strategy for enhancing the antitumor efficacy of pharmaceuticals. Current investigations on crystal engineering of antitumor agents are predominantly focused on organic small‐molecule drugs, whereas the correlation between crystal structure and bioactivity in inorganic nanomaterials remains underexplored. Herein, we report a comparative study on two crystalline polymorphs of manganese sulfide (MnS), α ‐MnS and γ ‐MnS, to unravel their distinct antitumor performances. Compared with γ ‐MnS, α ‐MnS demonstrates superior capacity in inducing intracellular reactive oxygen species (ROS) generation, leading to enhanced cytotoxicity against 4T1, A549, and MCF‐7 tumor cells. In a 4T1 tumor‐bearing mouse model, α ‐MnS treatment significantly reduces tumor volume relative to γ ‐MnS, while maintaining excellent biosafety profiles. These findings shed light on the structure–activity relationship of inorganic nanomaterials, providing a novel theoretical paradigm for the rational design of high‐performance nanotherapeutics with precise crystal form‐bioactivity matching.