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Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma
Fei Xie1, Jinrong Qiu1, Congyong Sun1
1The Comprehensive Cancer Center, Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
Abstract:
Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.
Insights
New aptamer-based nanomedicine targets esophageal squamous cell carcinoma (ESCC). This system delivers drugs and genes, inhibiting ESCC progression and metastasis for improved patient outcomes.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Esophageal squamous cell carcinoma (ESCC) presents a significant global health challenge with high mortality and limited targeted therapy options.
- Current treatment modalities for ESCC, including surgery, chemotherapy, and radiation, have not substantially improved the poor five-year survival rate, which remains below 20%.
Purpose of the Study:
- To develop an innovative aptamer-modified nanodelivery system for targeted inhibition of ESCC.
- To evaluate the efficacy of this system in delivering both chemotherapeutic drugs and gene silencing agents to ESCC cells.
Main Methods:
- Identification of a specific DNA aptamer (EA1) targeting ESCC cells using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX).
- Development of an aptamer-modified nano-system (EA1-EYLNs-PTX/siEFNA1) encapsulating paclitaxel (PTX) and small interfering RNA targeting Ephrin A1 (siEFNA1).
- Assessment of the nano-system's ability to inhibit ESCC proliferation, migration, invasion, and lung metastasis in vitro and in vivo.
Main Results:
- The EA1 aptamer demonstrated high specificity and affinity for ESCC cells.
- The EA1-EYLNs-PTX/siEFNA1 nano-system effectively delivered PTX and siEFNA1, significantly inhibiting ESCC tumor growth and metastasis.
- Ephrin A1 (EFNA1) was found to be overexpressed in metastatic ESCC tumors, correlating inversely with patient prognosis.
Conclusions:
- Aptamer-modified nanodelivery systems offer a promising strategy for targeted drug and gene delivery in ESCC.
- The developed EA1-EYLNs-PTX/siEFNA1 nano-system shows superior therapeutic efficacy against ESCC, potentially revolutionizing targeted therapy for this disease.
