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Symmetrical Tetravalent Aptamer-Protein Conjugate with Ultrahigh In Vivo Stability for Targeted Cancer Imaging and
Xiaotong Zhang1, Xueni Wang1, Qi Li1
1Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei230601, P. R. China.
Researchers developed a stable tetravalent aptamer-streptavidin conjugate (Tetra-XQ@SA) for enhanced cancer theranostics. This novel assembly improves drug delivery, tumor targeting, and antitumor efficacy, overcoming limitations of free aptamers.
Area of Science:
- Biotechnology
- Nanotechnology
- Oncology
Background:
- Clinical use of nucleic acid aptamers is limited by instability and poor targeting in vivo.
- Multivalent aptamer assemblies offer improved performance, but structural determinants of stability are not well understood.
Purpose of the Study:
- To fabricate a stable, symmetric tetravalent aptamer-streptavidin conjugate (Tetra-XQ@SA) for cancer theranostics.
- To elucidate the structure-stability relationship in aptamer assemblies for improved nuclease resistance and targeting.
Main Methods:
- Fabrication of a symmetric tetravalent aptamer-streptavidin conjugate (Tetra-XQ@SA).
- Assessment of nuclease resistance in DNase I and serum.
- Evaluation of binding affinity to CD71 receptors on cancer cells.
- In vitro doxorubicin loading and antitumor activity assays.
- In vivo studies for tumor retention and therapeutic efficacy.
Main Results:
- Tetra-XQ@SA demonstrated enhanced stability, withstanding 96 h in DNase I and 72 h in serum.
- The conjugate exhibited a 2-fold increase in binding affinity to CD71 receptors and 7-fold higher doxorubicin loading compared to free aptamers.
- In vivo studies showed prolonged tumor retention and achieved approximately 73% tumor inhibition.
Conclusions:
- Structural features like thymine bases, longer sequences, and double-stranded structures significantly enhance aptamer assembly stability.
- Tetra-XQ@SA represents a promising platform for targeted cancer therapy with improved stability and efficacy.
- This work provides insights into aptamer assembly design for overcoming clinical application challenges.
