Platform-based BST-2-targeted microbubbles enhance HIFU therapy and effectively inhibit prostate cancer residual growth

Objective This study aims to evaluate the potential of BST2-targeted microbubble-facilitated HIFU therapy for prostate cancer (PCa), and to elucidate the mechanisms of synergistic tumor suppression in residual lesions.Methods The specificity of BST-2 expression in PCa tumor endothelial cells was est...

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Main Authors: Hang Zhou, Jia Tang, Yujie Wan, Jiaqi Gong, Qizhi Wang, Kaifeng Huang, Ruixia Hong, Xinzhi Xu, Fang Li
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:International Journal of Hyperthermia
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Online Access:https://www.tandfonline.com/doi/10.1080/02656736.2025.2511035
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Summary:Objective This study aims to evaluate the potential of BST2-targeted microbubble-facilitated HIFU therapy for prostate cancer (PCa), and to elucidate the mechanisms of synergistic tumor suppression in residual lesions.Methods The specificity of BST-2 expression in PCa tumor endothelial cells was established using a cellular co-culture method. The targeting efficacy of Anti-BST-2 antibody-conjugated microbubbles (BST-2-MB) was evaluated both in vitro and in vivo. The therapeutic outcomes of BST-2-MB-augmented HIFU (High-Intensity Focused Ultrasound) for PCa in Balb/c mice were compared with those of non-targeted microbubbles and HIFU alone. Changes in the immunological microenvironment and modulation of BST-2-related oncogenic pathways in residual tumors were analyzed using Western Blot, immunofluorescence, flow cytometry, and ELISA.Results BST-2 is highly expressed in PCa vascular endothelial cells, and BST-2-MBs show strong targeting efficacy. HIFU combined with BST-2-MB achieved larger ablation volumes and potent inhibition of residual tumor growth. This treatment induced more immunogenic cell death (ICD), DC maturation, and CD8+ T cell infiltration, and significantly downregulated the expression of BST-2, EGFR, pSTAT3, and pErk1/2 compared to other treatments.Conclusion BST-2-MB combined with HIFU therapy demonstrates a superior synergistic antitumor effect in PCa, effectively inhibiting residual tumors, which offers a novel strategy to enhance HIFU efficacy.
ISSN:0265-6736
1464-5157