Ultrasound‐targeted microbubble destruction mediates <scp>PDE5i</scp>/<scp>NO</scp> integration for cavernosum remodeling and penile rehabilitation

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed the adverse remodeling of penis induced ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, therapeutic efficacy severely limited due poor accumulation under systemic medication endogenous nitric oxide (NO) deficiency Herein, innovative liposomal microbubble (MB) loaded with both Sildenafil (one PDE5i) NO was designed. Ultrasound-targeted MB destruction (UTMD)-mediated efficient release integration erectogenic agents into corpus cavernosum high biosafety. On a bilateral CNI rat model, multifunctional MB-cooperated UTMD improved perfusion penis, simultaneously, alleviated hypoxia oxidative stress, indicating successful activation NO–cyclic guanosine monophosphate pathway. Also, evaluation endothelial/muscular composition, intracavernosal pressure, neural integrity proved that coordinated intervention reversed abnormal structural promoted recovery functional erection. Our work demonstrates loading combined hold great promise “awaken” PDE5i neurogenic ED, which provided superior option ensuring rehabilitation.