A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer

Area of Science:

• Oncology
• Biotechnology
• Drug Delivery

Background:

• Esophageal cancer (EC) presents a poor prognosis with current treatments.
• Nucleolin (NCL) overexpression in tumors suggests it as a therapeutic target.
• Targeted therapies offer a promising strategy for esophageal cancer treatment.

Purpose of the Study:

• To design and prepare a novel aptamer-drug conjugate targeting Nucleolin (NCL) for esophageal cancer treatment.
• To evaluate the efficacy of the AS1411 aptamer-human serum albumin (HSA)-lidamycin (LDP)-active enediyne chromophore (AE) conjugate in vitro and in vivo.
• To assess the potential of this NCL-targeting conjugate as a novel therapeutic strategy for esophageal cancer.

Main Methods:

• Design and synthesis of the AS1411-HSA-LDP-AE aptamer-drug conjugate.
• In vitro studies involving esophageal cancer cell lines to assess binding, internalization, cytotoxicity, migration, invasion, and apoptosis.
• In vivo studies using a KYSE520 xenograft tumor nude mouse model to evaluate tumor targeting, enrichment, and anti-tumor efficacy.

Main Results:

• The AS1411-HSA-LDP conjugate demonstrated effective binding and internalization by esophageal cancer cells.
• In vivo studies showed targeted accumulation and prolonged retention of AS1411-HSA-LDP at the tumor site.
• AS1411-HSA-LDP-AE exhibited significant cytotoxicity, inhibited cell migration and invasion, induced apoptosis, and demonstrated a strong anti-tumor effect in vivo.

Conclusions:

• The novel NCL-targeting aptamer-drug conjugate, AS1411-HSA-LDP-AE, shows potent anti-tumor activity against esophageal cancer.
• This conjugate effectively targets and is internalized by esophageal cancer cells, accumulating in tumors.
• The developed conjugate represents a promising strategy for the targeted treatment of esophageal cancer.