Self-assembled aptamer-based drug carriers for bispecific cytotoxicity to cancer cells

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapeutics

Background:

• Monovalent aptamers offer specific drug delivery but struggle with cancer subtype heterogeneity.
• Clinical cancer samples exhibit biomarker diversity, limiting single aptamer recognition and effective targeting.
• A broader recognition range is crucial for aptamer-based cancer therapies to address patient variability.

Purpose of the Study:

• To develop a bispecific aptamer-based drug carrier with enhanced recognition capabilities for diverse cancer subtypes.
• To create a self-assembled drug delivery system capable of targeting multiple cancer cell populations simultaneously.
• To evaluate the efficacy of the bispecific carrier for targeted drug delivery and cytotoxicity in heterogeneous cancer models.

Main Methods:

• Self-assembly of two modified monovalent aptamers (sgc8c-sgd5a, SD) into a bispecific drug carrier.
• Loading of the anticancer drug doxorubicin (Dox) onto the self-assembled carrier (SD-Dox).
• Assessment of bispecific target cell binding, drug delivery, and cytotoxicity in mixed cell populations.

Main Results:

• The developed carrier (SD) demonstrated bispecific recognition, broadening targeting range compared to parent aptamers.
• SD facilitated simultaneous drug loading and exhibited bispecific binding and delivery of doxorubicin (Dox).
• SD-Dox induced significant bispecific cytotoxicity in target cancer cells within mixtures.

Conclusions:

• Bispecific aptamer-based drug carriers effectively address cancer subtype heterogeneity by broadening recognition capabilities.
• This approach enhances targeted drug delivery and cytotoxicity for clinically relevant heterogeneous cancer subtypes.
• The developed bispecific carrier shows promise for improving aptamer applications in cancer therapy.