Metastatic castration-resistant prostate cancer (mCRPC) is challenging to treat. Virus-like particles (VLPs), originating from JC polyomavirus (JCPyV) and carrying a suicide gene driven by the PSA promoter (PSAtk-VLPs), can inhibit tumor growth in animal models of human prostate cancer. However, the efficacy of suppression of orthotopic PCa growth and metastasis by PSAtk-VLPs remains undetermined. Here, we established an iRFP stable expression CRPC cell line suitable for deep-tissue observation using fluorescence molecular tomography (FMT). These cells were implanted into murine prostate tissue, and PSAtk-VLPs were systemically administered via the tail vein along with the prodrug ganciclovir (GCV), allowing for the real-time observation of orthotopic prostate tumor growth and CRPC tumor metastasis. Our findings demonstrated that systemic PSAtk-VLPs administration with GCV and subsequent FMT scanning facilitated real-time observation of the suppressed growth in mouse iRFP CRPC orthotopic tumors, which further revealed a notable metastasis rate reduction. Systemic PSAtk-VLPs and GCV administration effectively inhibited orthotopic prostate cancer growth and metastasis. These findings suggest the potential of JCPyV VLPs as a promising vector for mCRPC gene therapy. Conclusively, systemically administered JCPyV VLPs carrying a tissue-specific promoter, JCPyV VLPs can protect genes within the bloodstream to be specifically expressed in specific organs.

转移性去势抵抗性前列腺癌 (mCRPC) 的治疗具有挑战性。病毒样颗粒（VLP）源自 JC 多瘤病毒（JCPyV），携带由 PSA 启动子驱动的自杀基因（PSAtk-VLP），可以抑制人类前列腺癌动物模型中的肿瘤生长。然而，PSAtk-VLPs 抑制原位 PCa 生长和转移的功效仍未确定。在这里，我们建立了一种 iRFP 稳定表达 CRPC 细胞系，适合使用荧光分子断层扫描 (FMT) 进行深部组织观察。这些细胞被植入小鼠前列腺组织中，PSAtk-VLPs与前药更昔洛韦（GCV）一起通过尾静脉全身给药，从而可以实时观察原位前列腺肿瘤生长和CRPC肿瘤转移。我们的研究结果表明，全身性 PSAtk-VLP 联合 GCV 给药和随后的 FMT 扫描有助于实时观察小鼠 iRFP CRPC 原位肿瘤的抑制生长，这进一步揭示了转移率显着降低。全身性PSAtk-VLPs和GCV给药可有效抑制原位前列腺癌的生长和转移。这些发现表明 JCPyV VLP 作为 mCRPC 基因治疗的有前景载体的潜力。总之，全身施用携带组织特异性启动子的 JCPyV VLP，JCPyV VLP 可以保护血流中的基因在特定器官中特异性表达。