2. Academic Validation
  3. Harnessing prazosin for tumors: Liposome hybrid nanovesicles activate tumor immunotherapy via autophagy inhibition

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

  • Biomaterials. 2025 Aug:319:123184. doi: 10.1016/j.biomaterials.2025.123184.
Xinyang Xuanyuan 1,  Wenshang Liu 2,  Min Jiang 3,  Xin Zhang 4,  BeiBei Wen 5,  Rui Zheng 4,  Ning Yao 6,  Tinglin Zhang 7,  Yu Feng 5,  Chaofeng Qiao 5,  Huiqi Zhang 5,  Dong Luo 5,  Sa Feng 8,  Meng Li 9,  Jie Gao 10,  Zhengmao Lu 11
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
  • 2 Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 3 The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
  • 4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
  • 5 School of Pharmacy, Henan University, Kaifeng, 475004, China.
  • 6 Department of General Surgery, Joint Support Force 903rd Hospital, Hangzhou, 310013, China.
  • 7 Changhai Clinical Research Unit, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
  • 8 School of Pharmacy, Henan University, Kaifeng, 475004, China. Electronic address: [email protected].
  • 9 Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: [email protected].
  • 10 Changhai Clinical Research Unit, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, 200433, China. Electronic address: [email protected].
  • 11 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China. Electronic address: [email protected].
PMID: 39985978 DOI: 10.1016/j.biomaterials.2025.123184
Abstract

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.

Keywords

Antigen cross-Presentation; Autophagy inhibition; Immunogenic cell death; Prazosin-liposome hybrid nanovesicles; Tumor immunotherapy.

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