Effect of Engineered Cyanobacterial Capsules on a Neurogenic Bladder after Spinal Cord Injury

Abstract

The presence of a neurogenic bladder is a severe but common complication of spinal cord injury (SCI). Multiple pathological factors, such as hypoxia, ischemia, and oxidative stress caused by SCI, promote M1 microglial polarization and the release of proinflammatory factors to amplify inflammation. An excessive inflammatory response stimulates the generation of reactive oxygen species (ROS) and induces oxidative stress to promote neuronal ferroptosis, thus leading to bladder dysfunction after SCI. Therefore, promoting the recovery of neural function by regulating the interaction between microglia and neurons is important. For this purpose, we developed an engineered immunoregulatory cyanobacterial capsule named siRNA@Cyanzyme, which consists of MnO₂@zeolitic-imidazolate framework@cyanobacteria (Cyanzyme) and a small-interfering RNA targeting ACSL4 (siRNA-ACSL4). Cyanzyme reversed M1 microglial polarization via photosynthetic oxygen to promote anti-inflammatory factor release. MnO₂ nanoenzymes grown on the surface of ZIF-8 eliminated excessive ROS to reduce oxidative stress. Moreover, Cyanzyme increased the delivery efficiency of siRNA-ACSL4, which is a key regulator of ferroptosis. Both treatments alleviated GABAergic neuron damage to mitigate bladder dysfunction. Our data demonstrated that siRNA@Cyanzyme effectively reversed M1 microglial polarization, reduced neuronal ferroptosis, and ultimately restored neurogenic bladder function.