Chen Mei, Guo Jinjuan, Xu Bing
Department of Pharmacy, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
Department of Pharmacy, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China.
J Fluoresc. 2025 Jun 13. doi: 10.1007/s10895-025-04392-x.
Cervical squamous cell carcinoma (CSCC) remains one of the leading causes of cancer-related deaths among women. In advanced stages, treatment is often hindered by drug resistance and severe toxic side effects. The solute carrier protein PCNA, a key regulatory factor in the cystine/glutamate antiporter system, promotes tumor progression by maintaining cellular redox balance and inhibiting ferroptosis, making it a highly promising therapeutic target. In this study, a fluorescence detection platform based on a chitosan (CS)-modified cobalt(II) coordination polymer (CP1) was developed for the highly sensitive detection of PCNA activity. By loading cyclic peptide compound 1, the platform also achieves dual diagnostic and therapeutic functions (CS@CP1@1). Upon interaction with PCNA, the fluorescence intensity of the probe is significantly reduced due to the specific binding between CP1 and PCNA enabling precise fluorescence signal response. The developed sensing platform exhibits a broad linear detection range (0.5-60 U/L) and an ultra-low limit of detection (LOD = 0.14 U/L). Cell experiments further confirmed that this system effectively inhibits PCNA activity and significantly reduces the proliferation of CSCC cells, demonstrating promising therapeutic potential.
宫颈鳞状细胞癌（CSCC）仍然是女性癌症相关死亡的主要原因之一。在晚期，治疗常常受到耐药性和严重毒副作用的阻碍。溶质载体蛋白PCNA是胱氨酸/谷氨酸反向转运体系统中的关键调节因子，通过维持细胞氧化还原平衡和抑制铁死亡促进肿瘤进展，使其成为一个极具前景的治疗靶点。在本研究中，开发了一种基于壳聚糖（CS）修饰的钴（II）配位聚合物（CP1）的荧光检测平台，用于高灵敏度检测PCNA活性。通过负载环肽化合物1，该平台还实现了双重诊断和治疗功能（CS@CP1@1）。与PCNA相互作用时，由于CP1与PCNA之间的特异性结合，使探针的荧光强度显著降低，从而实现精确的荧光信号响应。所开发的传感平台具有宽线性检测范围（0.5 - 60 U/L）和超低检测限（LOD = 0.14 U/L）。细胞实验进一步证实，该系统有效抑制PCNA活性并显著降低CSCC细胞的增殖，显示出有前景的治疗潜力。
