Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

中文翻译：

---

在离体和体内模型中通过图像引导的可注射离子液体进行前列腺组织消融和药物输送


良性前列腺增生和前列腺癌通常与下尿路症状相关，这会严重影响患者的生活质量。为了应对这一挑战，我们开发并优化了一种可注射化合物——前列腺消融和药物递送剂（PADA），用于经皮前列腺组织消融并同时递送治疗剂。 PADA 是一种由胆碱和香叶酸与抗癌药物和造影剂混合而成的离子液体。 PADA 配方针对与手注射兼容的机械性能、扩散能力、针对前列腺细胞的细胞毒性以及 X 射线造影剂的可见度进行了优化。 PADA 还在体外对临床分离的高度耐药细菌表现出抗菌特性。在健康猪、犬和人类前列腺以及新切除的人类肿瘤中，对超声引导注射、PADA 在组织中的分散和组织消融进行了离体测试。在小鼠皮下肿瘤模型和犬前列腺中进行体内测试。在所有模型中，PADA 减少了分散区域中活细胞的数量，并支持纳武单抗在整个组织中的递送。在犬类生存实验中，没有出现不良事件，也不影响排尿。注射方法在超声引导下很容易进行，并产生局部效果，且安全性良好。这些发现表明，PADA 是一种有前途的治疗性前列腺消融策略，用于治疗下尿路症状。