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. 2021 Sep 21;15:3985-3996. doi: 10.2147/DDDT.S322854. eCollection 2021.
The sensitive and specific detection of pathogenic cells is important in tumor diagnosis at an early stage. Aptamers are short single-stranded oligonucleotides evolved from systematic evolution of ligands by exponential enrichment (SELEX). It has been proved that aptamers can interact with cognate target molecules with high affinity and specificity and have great potential in the development of medical imaging at molecular level.
To select epithelial cell adhesion molecule (EpCAM) specific aptamers targeting prostate cancer and further to conjugate aptamers with GoldMag nanoparticles (a typical iron oxide core/gold shell structure) to construct magnetic molecular probes for medical imaging.
EpCAM-specific aptamers were selected by Cell-SELEX. The enrichment of specific aptamer candidates was monitored by flow cytometric analysis. Aptamers were further conjugated with GoldMag nanoparticles to construct magnetic molecular probes. The affinity and specificity of aptamer candidates and aptamer-conjugated GoldMag nanoparticles were evaluated. The MR imaging of aptamer-conjugated GoldMag nanoparticles to prostate cancer was further explored in vitro and in vivo.
After 12 rounds of selection, aptamer candidates Eppc6 and Eppc14 could specifically target three types of prostate cancer cells, revealing a high affinity of Eppc6 and Eppc14. Moreover, aptamer-conjugated GoldMag nanoparticles not only exhibited good affinity to different prostate cancer cells but also produced strong T2WI signal intensity reduction distinguished from peritumoral tissue in MRI, indicating that the molecular probes possess both the affinity properties of EpCAM-specific aptamer and the superparamagnetic features of iron oxide.
Our study indicates that aptamer Eppc6 and Eppc14 can recognize prostate cancer cells and tissues. The aptamer-conjugated GoldMag nanoparticles constructed in the study can be used as a molecular imaging agent for detection of PCa in MRI.
在肿瘤的早期诊断中，对致病细胞进行敏感和特异的检测非常重要。适体是从配体指数富集系统进化（SELEX）中衍生出来的短链单链寡核苷酸。已经证明，适体能与同源靶分子高亲和力和特异性相互作用，在分子水平的医学成像发展方面具有巨大潜力。
筛选针对前列腺癌的上皮细胞黏附分子（EpCAM）特异性适体，并进一步将适体与 GoldMag 纳米颗粒（一种典型的氧化铁核/金壳结构）缀合，构建用于医学成像的磁性分子探针。
通过细胞 SELEX 筛选 EpCAM 特异性适体。通过流式细胞术分析监测特异性适体候选物的富集情况。进一步将适体与 GoldMag 纳米颗粒缀合，构建磁性分子探针。评估适体候选物和适体缀合的 GoldMag 纳米颗粒的亲和力和特异性。进一步在体外和体内探索适体缀合的 GoldMag 纳米颗粒对前列腺癌的磁共振成像。
经过 12 轮筛选，适体候选物 Eppc6 和 Eppc14 能够特异性靶向三种类型的前列腺癌细胞，显示出 Eppc6 和 Eppc14 的高亲和力。此外，适体缀合的 GoldMag 纳米颗粒不仅对不同的前列腺癌细胞表现出良好的亲和力，而且在 MRI 中产生了与肿瘤周围组织明显不同的强 T2WI 信号强度降低，表明该分子探针既具有 EpCAM 特异性适体的亲和力特性，又具有氧化铁的超顺磁性特征。
本研究表明适体 Eppc6 和 Eppc14 可以识别前列腺癌细胞和组织。本研究构建的适体缀合的 GoldMag 纳米颗粒可用作 MRI 中检测前列腺癌的分子成像剂。
