Harnessing prazosin for tumors: Liposome hybrid nanovesicles activate tumor immunotherapy via autophagy inhibition

Prazosin (Prz), an antagonist of alpha-1 adrenergic receptors, is conventionally employed in the treatment of hypertension. Our study pioneers the exploration of Prz in oncology, examining its impact on cellular autophagy and its potential to trigger antitumor immune responses. We have developed a novel Prz-loaded liposome hybrid nanovesicle (Prz@LINV) system, integrating tumor-derived nanovesicles (TNV) with liposomes (LIP) to facilitate targeted Prz delivery to tumor sites. This formulation enhances Prz bioavailability and markedly inhibits tumor cell autophagy, leading to immunogenic cell death (ICD) and the activation of antitumor immune responses. Furthermore, Prz@LINV modulates dendritic cells (DCs), augmenting their antigen cross-presentation capacity and thereby potentiating antitumor immunity. These effects were validated in a colorectal cancer mouse model, demonstrating the good biocompatibility of Prz@LINV and its significant inhibition in tumor growth, along with the enhancement of antitumor immune responses. Our findings elucidate a novel mechanism by which Prz inhibits autophagy and enhances the antitumor immune response, providing a foundation for the development of innovative immunotherapeutic strategies. The efficacy of Prz@LINV suggests that Prz may emerge as a pivotal component in future immunotherapeutic regimens, offering patients more potent therapeutic options.