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Development of a DNA Aptamer against Multidrug-Resistant Hepatocellular Carcinoma for In Vivo Imaging
Lin Zhang1, Lingli Zhou1, Hui Zhang1
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
Abstract:
Hepatocellular carcinoma (HCC) is a type of cancer that has high rates of recurrence and mortality. One of the most important factors that lead to treatment failure of HCC is the acquisition of multidrug resistance (MDR). Development of specific ligands for multidrug-resistant HCC will provide useful molecular tools for precise diagnosis and targeted theranostics. Herein, a multidrug-resistant HCC cell (HepG2/MDR)-specific aptamer was developed through Cell-SELEX (systematic evolution of ligands by exponential enrichment) technology. With dissociation constants lying in the nanomolar range, the molecularly designed PS-ZL-7c aptamer showed great selectivity to drug-resistant cancer cells. The in vivo imaging results illustrated that the PS-ZL-7c specifically accumulated in the drug-resistant tumors but not in drug-sensitive tumors and normal tissues, indicating that the PS-ZL-7c aptamer possessed excellent potential as a targeting ligand for precise diagnosis and target theranostics of multidrug-resistant HCC.
Insights
Researchers developed a novel aptamer, PS-ZL-7c, that specifically targets multidrug-resistant hepatocellular carcinoma (HCC). This molecular tool shows promise for precise diagnosis and targeted theranostics in treating drug-resistant liver cancer.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) presents high recurrence and mortality rates.
- Multidrug resistance (MDR) is a major factor in HCC treatment failure.
- Targeted molecular tools are needed for precise diagnosis and theranostics of MDR-HCC.
Purpose of the Study:
- To develop a specific aptamer for targeting multidrug-resistant HCC cells.
- To evaluate the aptamer's selectivity and diagnostic potential.
- To assess the aptamer's efficacy in vivo for targeted theranostics.
Main Methods:
- Systematic evolution of ligands by exponential enrichment (Cell-SELEX) technology was employed.
- Aptamer PS-ZL-7c was designed and synthesized.
- In vitro selectivity assays and in vivo imaging studies were conducted.
Main Results:
- The PS-ZL-7c aptamer demonstrated high selectivity for multidrug-resistant HCC cells (HepG2/MDR).
- Dissociation constants were in the nanomolar range, indicating strong binding affinity.
- In vivo imaging confirmed specific accumulation in drug-resistant tumors, sparing sensitive tumors and normal tissues.
Conclusions:
- The PS-ZL-7c aptamer is a highly specific and effective targeting ligand for multidrug-resistant HCC.
- This aptamer holds significant potential for precise diagnosis and targeted theranostics of MDR-HCC.
- The findings pave the way for improved therapeutic strategies against resistant liver cancer.
