Department of Radiology, The Second Affiliated Hospital, Xi' an Jiaotong University, Xi'an, Shaanxi Province, 710004, People's Republic of China.
Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, People's Republic of China.
Drug Des Devel Ther. 2024 Mar 18;18:859-870. doi: 10.2147/DDDT.S444988. eCollection 2024.
Early recognition of castration-resistant state is of significance for timely adjustment of treatment regimens and improvement of prognosis.
This study aims to screen new aptamers CRda8 and CRda21 which recognize castration resistant prostate cancer (CRPC) cells with high affinity and specificity by SELEX technology.
The enrichment of specific aptamer candidates was monitored by flow cytometric analysis. The affinity and specificity of aptamer candidates were evaluated by flow cytometry and immunofluorescence assay. MR imaging of CRda21-conjugated polyethylene glycol (PEG)-FeO nanoparticles to CRPC was further explored in vivo.
Both aptamers showed high specificity to target cells with dissociation constants in the nanomolar range, and did not recognize other tested cells. The staining of clinical tissue sections with fluorescent dye labeled aptamers showed that sections from CRPC exhibited stronger fluorescence while sections from benign prostatic hyperplasia and androgen dependent prostate cancer did not exhibit notable fluorescence. In vivo MRI demonstrated that CRda21-conjugated PEG-FeO had good affinity to CRPC and produced strong T2WI signal intensity reduction distinguished from peritumoral tissue.
The high affinity and specificity of CRda8 and CRda21 make the aptamer hold potential for early recognition of castration-resistant state and diagnosis of CRPC at the cellular level.
早期识别去势抵抗状态对于及时调整治疗方案和改善预后具有重要意义。
本研究旨在通过 SELEX 技术筛选出能够高亲和力和特异性识别去势抵抗性前列腺癌（CRPC）细胞的新型适体 CRda8 和 CRda21。
通过流式细胞术分析监测特异性适体候选物的富集情况。通过流式细胞术和免疫荧光分析评估适体候选物的亲和力和特异性。进一步探讨了 CRda21 偶联聚乙二醇（PEG）-FeO 纳米颗粒对 CRPC 的磁共振成像。
两种适体均表现出对靶细胞的高特异性，解离常数在纳摩尔范围内，且不识别其他测试细胞。用荧光染料标记的适体对临床组织切片进行染色显示，CRPC 组织切片显示出更强的荧光，而良性前列腺增生和雄激素依赖性前列腺癌组织切片则没有明显的荧光。体内 MRI 显示，CRda21 偶联的 PEG-FeO 对 CRPC 具有良好的亲和力，并产生强烈的 T2WI 信号强度降低，与肿瘤周围组织区分开来。
CRda8 和 CRda21 的高亲和力和特异性使适体具有在细胞水平上早期识别去势抵抗状态和诊断 CRPC 的潜力。
