👤 Authors: Shi-Jie Hao, Xiejunhao Zheng, Shun-Yu Wu, Zitong Wang, Tiange Wu, Yanli An, Han Guan, Zihao Wang, Shen Zhang, Wei Yang, Gao-Jun Teng, Bin Xu, Fu-Gen Wu
Dual Neuromodulation Remodels Neuro-Immune Crosstalk and Chemokine Network for Combating Postoperative Progression of Prostate Cancer.
The autonomic nerves drive prostate cancer (PCa) progression, yet a strategy for dual modulation of sympathetic and parasympathetic nerves remains undeveloped. Here, building on the multicenter clinical findings, we develop a personalized nanotechnology-enabled dual neurotherapy (denoted as ADNT) for PCa.
The ADNT employs hybrid nanovesicles composed of autologous tumor cell membranes and functionalized liposomes to codeliver the β-blocker and the muscarinic receptor antagonist to autonomic nerves in residual tumor. In refractory, highly invasive, and orthotopic murine PCa models, the ADNT effectively delays postoperative recurrence and metastasis.
Light-sheet fluorescence microscopy visually confirms the downregulation of autonomic nerve infiltration. Cytometry by time-of-flight reveals that ADNT remodels neuro-immune crosstalk and the chemokine network, promoting antitumor immune response and suppressing tumor progression.
Additionally, ADNT also alleviates cancer-associated cachexia and anxiety. Combined with immune checkpoint blockade, ADNT induces complete responses in 100% of mice.
Immunofluorescence staining of human PCa specimens confirms the clinical translatability of ADNT, establishing ADNT as a promising therapeutic strategy for PCa.
