Targeted Fluorescent Polysaccharide Platform for Solute Carrier Protein PCNA Detection and Cervical Squamous Cell Carcinoma Inhibition.

Abstract

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.