A Dual-Targeting Circular Aptamer Strategy Enables the Recognition of Different Leukemia Cells with Enhanced Binding...

Area of Science:

• Biotechnology
• Molecular Biology
• Oncology

Background:

• Monovalent aptamers in oncology show limitations in cancer cell recognition and internalization due to limited cell surface receptors.
• A narrow recognition spectrum restricts the effectiveness of current aptamer-based therapies.

Purpose of the Study:

• To develop a dual-targeting circular aptamer (DTCA) for enhanced recognition of cancer cells.
• To improve aptamer-receptor interactions, binding, and internalization for better therapeutic outcomes.
• To expand the recognition spectrum of aptamers for diverse leukemia cell types.

Main Methods:

• Development of a dual-targeting circular aptamer (DTCA) capable of recognizing two distinct biomarkers on living cells.
• Application of an enzyme-promoted terminal ligation strategy to enhance DTCA stability in serum.
• Chemical incorporation of 5-fluorodeoxyuridine into DTCA to create a pharmaceutically functional aptamer.

Main Results:

• DTCA demonstrated augmented aptamer-receptor interactions, leading to enhanced recognition and internalization in target cells.
• The DTCA exhibited an expanded recognition spectrum, effectively targeting various leukemia cell types.
• The modified DTCA showed significant stability in serum and high cytotoxicity against cancer cells, with minimal impact on normal cells.
• Precise tumor-imaging capabilities were achieved, validating the strategy's efficacy.

Conclusions:

• The developed DTCA offers a superior strategy for cancer therapy by enhancing target cell recognition and drug delivery.
• DTCA exhibits excellent selectivity and stability, paving the way for more effective and targeted cancer treatments.
• This dual-targeting approach significantly improves upon monovalent aptamer limitations in oncology.