Sun Jian-Xuan, Xia Qi-Dong, Xu Jin-Zhou, An Ye, Ma Si-Yang, Xu Jing-Yu, Xiang Jia-Cheng, Liu Chen-Qian, Xu Meng-Yao, Zhang Si-Han, Luan Yang, Tang Ke, Wang Shao-Gang
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, USA.
J Control Release. 2025 Apr 10;380:199-218. doi: 10.1016/j.jconrel.2025.01.079. Epub 2025 Feb 5.
Radical prostatectomy with pelvic lymph node dissection is the best treatment for intermediate- to high-risk localized prostate cancer (PCa). However, conventional white light surgery has difficulties in identifying tumor boundary and micrometastases intraoperatively. Fluorescence guided surgery (FGS) can solve the above difficulties, but lacks tumor-specific near-infrared fluorescent (NIRF) probes in PCa. STEAP1 was an ideal target in PCa treatment and imaging. Here, we constructed a PCa specific fluorescent probe based on extracellular vesicles targeting STEAP1 (AS-EVs) loaded with NIRF dye S0456 and evaluated its preclinical profiles. In vitro and in vivo studies both showed S0456@AS-EVs was safe and showed strong targeting ability to PCa in various mice xenograft models. S0456@AS-EVs could clear rapidly from blood (half-time of 4.29 h) and retain in the STEAP1 positive tumor tissues for more than 72 h with the highest tumor background ratio (TBR) of 3:1, which was superior to ICG, free S0456, ICG@Ctrl-EVs and S0456@Ctrl-EVs (p < 0.01). Finally, S0456@AS-EVs was applied in FGS on intramuscular model, and the tumors were resected under white light and fluorescence respectively. Compared with white light surgery, mice undergoing FGS had lower positive margin rate and better postoperative survival (p = 0.0342).
根治性前列腺切除术联合盆腔淋巴结清扫术是治疗中高危局限性前列腺癌（PCa）的最佳方法。然而，传统的白光手术在术中识别肿瘤边界和微转移方面存在困难。荧光引导手术（FGS）可以解决上述难题，但在PCa中缺乏肿瘤特异性近红外荧光（NIRF）探针。STEAP1是PCa治疗和成像的理想靶点。在此，我们构建了一种基于靶向STEAP1的细胞外囊泡（AS-EVs）的PCa特异性荧光探针，其负载了NIRF染料S0456，并评估了其临床前特征。体外和体内研究均表明，S0456@AS-EVs安全，在各种小鼠异种移植模型中对PCa具有强大的靶向能力。S0456@AS-EVs可迅速从血液中清除（半衰期为4.29小时），并在STEAP1阳性肿瘤组织中保留超过72小时，最高肿瘤背景比（TBR）为3:1，优于吲哚菁绿（ICG）、游离S0456、ICG@对照细胞外囊泡（Ctrl-EVs）和S0456@Ctrl-EVs（p < 0.01）。最后，将S0456@AS-EVs应用于肌肉模型的FGS中，并分别在白光和荧光下切除肿瘤。与白光手术相比，接受FGS的小鼠切缘阳性率更低，术后生存率更高（p = 0.0342）。
