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Optimization of Short RNA Aptamers for TNBC Cell Targeting
Simona Camorani1, Annachiara d'Argenio1, Lisa Agnello1,2
1National Research Council (CNR), Institute of Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS), 80131 Naples, Italy.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive cancer with limited targeted therapies. RNA aptamers, suitably chemically modified, work for therapeutic purposes in the same way as antibodies. We recently generated 2'Fluoro-pyrimidines RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells. Here, we optimized three of them by shortening and proved the truncated aptamers as optimal candidates to enable active targeting to TNBC. By using prediction of secondary structure to guide truncation, we identified structural regions that account for the binding motifs of the full-length aptamers. Their chemical synthesis led to short aptamers with superb nuclease resistance, which specifically bind to TNBC target cells and rapidly internalize into acidic compartments. They interfere with the growth of TNBC cells as mammospheres, thus confirming their potential as anti-tumor agents. We propose sTN145, sTN58 and sTN29 aptamers as valuable tools for selective TNBC targeting and promising candidates for effective treatments, including therapeutic agents and targeted delivery nanovectors.
Insights
Researchers developed short RNA aptamers for targeting triple-negative breast cancer (TNBC). These aptamers show promise as anti-tumor agents and for targeted drug delivery in TNBC treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive with few targeted treatments.
- RNA aptamers offer therapeutic potential similar to antibodies.
- Previous work generated 2'Fluoro-pyrimidines RNA aptamers for TNBC recognition.
Purpose of the Study:
- To optimize and validate truncated RNA aptamers for active targeting of TNBC.
- To identify structural regions responsible for binding motifs in full-length aptamers.
Main Methods:
- Secondary structure prediction guided aptamer truncation.
- Chemical synthesis of short, nuclease-resistant aptamers.
- In vitro binding and internalization assays with TNBC cells.
- Assessment of aptamer effects on TNBC mammosphere growth.
Main Results:
- Truncated aptamers (sTN145, sTN58, sTN29) demonstrated specific binding to TNBC cells.
- Aptamers were rapidly internalized into acidic cellular compartments.
- Short aptamers effectively inhibited TNBC cell growth in mammosphere models.
- Optimized aptamers exhibited high nuclease resistance.
Conclusions:
- Short RNA aptamers are effective for selective TNBC targeting.
- These aptamers show potential as anti-tumor agents for TNBC.
- The aptamers are promising candidates for therapeutic applications and targeted nanovectors in TNBC treatment.
