An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells

Area of Science:

• Oncology
• Biotechnology
• Drug Delivery

Background:

• Liver cancer lacks effective therapies, leading to poor patient survival.
• Cancer stem-like cells drive tumor initiation, progression, metastasis, and treatment resistance.
• Targeting cancer stem-like cells is crucial for developing effective liver cancer treatments.

Purpose of the Study:

• To develop and evaluate a novel drug delivery system targeting CD133+ liver cancer stem cells.
• To assess the efficacy of doxorubicin-loaded aptamers against CD133 (CD133-apt-Dox) in preclinical models.

Main Methods:

• Development of a CD133-specific aptamer (CD133-apt) and loading it with doxorubicin (Dox).
• In vitro and in vivo studies using liver cancer cell lines, patient-derived organoids, and mouse models (xenograft and DEN-induced).
• Evaluation of drug delivery, cancer stem cell properties, tumor growth inhibition, and therapeutic effects.

Main Results:

• CD133-apt efficiently delivered doxorubicin to CD133-expressing liver cancer cells with enhanced accumulation.
• CD133-apt-Dox treatment impaired cancer stem cell self-renewal and stemness phenotypes.
• Significant inhibition of liver cancer cell growth, organoid proliferation, and tumor growth in both xenograft and immunocompetent mouse models was observed.

Conclusions:

• Aptamer-mediated targeting of CD133 represents a highly promising strategy for liver cancer therapy.
• CD133-apt-Dox effectively targets and eliminates liver cancer stem cells, offering a potential breakthrough in treatment.
• This approach holds significant potential for improving outcomes in liver cancer patients.