Self‐Propelled HPB@Lip@AB Nanomotors Ameliorate Dry Eye Disease

ABSTRACT Dry eye disease (DED) is a common ocular surface disorder closely associated with mitochondrial dysfunction and excessive accumulation of reactive oxygen species (ROS). However, existing treatments are limited by ocular surface barriers. This study developed an integrated nanomotor‐based eye drop system (HPB@Lip@AB) combining self‐propulsion, mitochondrial repair, and multiple antioxidant functions. The nanomotor consists of a hollow Prussian blue (HPB) nanozyme core loaded with ammonia borane (AB) as a molecular hydrogen (H 2 ) precursor, encapsulated within a liposomal shell to form a core–shell structure. In the DED microenvironment, HPB catalyzes the decomposition of hydrogen peroxide (H 2 O 2 ) to generate oxygen bubbles, propelling the nanomotors to rapidly penetrate the tear film barrier. Following cellular uptake, AB is proposed to generate H 2 in acidic intracellular environments, potentially acting synergistically with HPB to exert antioxidant, anti‐apoptotic, and anti‐inflammatory effects. This restores tear secretion, stabilizes the tear film, and repairs the corneal epithelium. H 2 ‐related effects were associated with increased aldehyde dehydrogenase 1 family member L2 (ALDH1L2) expression, improved mitochondrial function, and reduced apoptosis and inflammation. Our nanomotor strategy enables efficient DED treatment through combined mechanisms, offering a promising platform for high‐penetration ocular drug delivery.