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Targeted Fluorescent Polysaccharide Platform for Solute Carrier Protein PCNA Detection and Cervical Squamous Cell
Mei Chen1, Jinjuan Guo2, Bing Xu3
1Department of Pharmacy, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
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.
Insights
A novel fluorescence detection platform targets PCNA (proliferating cell nuclear antigen) to combat cervical squamous cell carcinoma (CSCC). This system shows promise in inhibiting cancer cell growth and offers dual diagnostic and therapeutic capabilities.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Cervical squamous cell carcinoma (CSCC) poses a significant health threat to women, with advanced stages facing challenges in treatment due to drug resistance and toxicity.
- Proliferating cell nuclear antigen (PCNA) is a key regulator in tumor progression, maintaining redox balance and inhibiting ferroptosis, making it a critical therapeutic target.
Purpose of the Study:
- To develop a highly sensitive fluorescence detection platform for PCNA activity.
- To create a dual-function system for diagnosing and treating CSCC by targeting PCNA.
Main Methods:
- Fabrication of a chitosan-modified cobalt(II) coordination polymer (CP1) based fluorescence probe.
- Loading of cyclic peptide compound 1 onto the probe for dual diagnostic and therapeutic functions (CS@CP1@1).
- Utilizing the specific interaction between CP1 and PCNA to modulate fluorescence intensity for detection.
Main Results:
- The developed sensing platform demonstrated high sensitivity for PCNA activity detection with a broad linear range (0.5-60 U/L) and a low limit of detection (0.14 U/L).
- The CS@CP1@1 system effectively inhibited PCNA activity in cell experiments.
- Significant reduction in CSCC cell proliferation was observed, indicating therapeutic potential.
Conclusions:
- The developed fluorescence platform offers a sensitive method for PCNA activity detection.
- The dual-function CS@CP1@1 system shows promise for the diagnosis and treatment of CSCC by targeting PCNA and inhibiting tumor cell proliferation.
