Huang Zhidie, Li Pinghui, Li Yiwen, Duan Xiaoyan, Li Mengting, Jiang Dawei, Li Jianbo
Inner Mongolia Medical University, Hohhot, People's Republic of China.
Department of Nuclear Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People's Republic of China.
Int J Nanomedicine. 2025 Mar 19;20:3595-3606. doi: 10.2147/IJN.S510964. eCollection 2025.
SYL3C is an optimized DNA aptamer with high selectivity and affinity for the epithelial cell adhesion molecule (EpCAM), an overexpressed tumor antigen in colorectal cancer (CRC). While its cellular affinity has been validated, in vivo studies are lacking.
This study modifies SYL3C with the fluorescent motif Cy7 to evaluate its metabolism and diagnostic potential in EpCAM-positive HT-29 xenograft mice using near-infrared fluorescence (NIRF). We also employ DNA Tetrahedra (DTN) to load the Cy7-DTN-SYL3C probe and assess whether this strategy improves circulation and tumor uptake of SYL3C.
Cy7-SYL3C is primarily metabolized by the kidneys and enables targeted imaging of HT-29 tumors, outperforming untargeted Cy7-DTN. The DTN coupling strategy prolongs SYL3C metabolism and enhances tumor probe uptake about twice higher than Cy7-SYL3C over 24 hours.
This study presents preliminary evidence for the SYL3C aptamer's potential in vivo imaging of EpCAM-positive CRC. The DTN conjugation strategy may extend the aptamer's metabolic stability and improve tumor uptake, expanding its applications in CRC diagnosis and treatment.
SYL3C是一种经过优化的DNA适配体，对上皮细胞粘附分子（EpCAM）具有高选择性和亲和力，EpCAM是结直肠癌（CRC）中一种过表达的肿瘤抗原。虽然其细胞亲和力已得到验证，但缺乏体内研究。
本研究用荧光基序Cy7修饰SYL3C，以使用近红外荧光（NIRF）评估其在EpCAM阳性HT-29异种移植小鼠中的代谢和诊断潜力。我们还采用DNA四面体（DTN）来负载Cy7-DTN-SYL3C探针，并评估该策略是否能改善SYL3C的循环和肿瘤摄取。
Cy7-SYL3C主要通过肾脏代谢，并能够对HT-29肿瘤进行靶向成像，其表现优于非靶向的Cy7-DTN。DTN偶联策略延长了SYL3C的代谢，并在24小时内增强了肿瘤对探针的摄取，比Cy7-SYL3C高出约两倍。
本研究为SYL3C适配体在EpCAM阳性CRC的体内成像潜力提供了初步证据。DTN偶联策略可能会延长适配体的代谢稳定性并改善肿瘤摄取，扩大其在CRC诊断和治疗中的应用。
