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Published on: February 3, 2015
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.
Abstract:
The clinical application of nucleic acid aptamers is hindered by rapid degradation and poor targeting in physiological conditions. Multivalent assembly can improve their performance, yet key structural rules for stability are not fully clarified. Here, we fabricate a symmetric tetravalent aptamer-streptavidin conjugate (Tetra-XQ@SA) for cancer theranostics with greatly enhanced stability. Thymine bases, longer sequences, and double-stranded structures collectively strengthen its nuclease resistance, enabling stable storage for 96 h in DNase I and 72 h in serum. Compared with free aptamers, Tetra-XQ@SA shows 2-fold higher binding affinity to cancer cell CD71 receptors, 7-fold greater doxorubicin loading, and improved antitumor activity. It achieves prolonged tumor retention and an ∼73% tumor inhibition rate in vivo. This study reveals the structure-stability relationship of aptamer assemblies and offers a versatile platform for targeted cancer therapy.
