Cell-SELEX-based selection of aptamers that recognize distinct targets on metastatic colorectal cancer cells

Area of Science:

• Biotechnology
• Molecular Biology
• Cancer Research

Background:

• Improving survival rates for cancer patients necessitates advanced diagnostic and therapeutic strategies targeting metastasis.
• Metastasis-related molecular targets are crucial for developing effective cancer treatments.

Purpose of the Study:

• To select metastatic-specific aptamers for colorectal cancer (CRC) using subtractive Cell-SELEX.
• To functionalize selected aptamers for targeted drug delivery and molecular imaging applications.
• To demonstrate the potential of aptamer panels for combined diagnostic and therapeutic use.

Main Methods:

• Subtractive Cell-SELEX was employed using highly metastatic CRC LoVo cells and non-metastatic HCT-8 cells.
• Seven aptamers with high specificity and nanomolar binding affinity (Kd) to target cells were identified.
• Individual aptamers were functionalized for drug delivery (W14 with doxorubicin) and imaging (W3 with quantum dots).

Main Results:

• Aptamers demonstrated highly specific binding to metastatic CRC cells.
• Aptamer W14 facilitated targeted doxorubicin delivery, reducing off-target cytotoxicity.
• Aptamer W3 enabled targeted imaging of metastatic cancer cell lines, murine tissues, and patient tissues.
• Selected aptamers showed no mutual binding interference, allowing for combined use.

Conclusions:

• Single Cell-SELEX can yield a panel of aptamers recognizing distinct molecular features of target cells.
• Functionalized aptamers offer potential for individualized applications in cancer therapy and diagnostics.
• The developed aptamers can be utilized in combination for enhanced metastatic cancer management.