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Self-Assembled Aptamer-Based Drug Carriers for Bispecific Cytotoxicity to Cancer Cells

Authors

  • Guizhi Zhu,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
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  • Dr. Ling Meng,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
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  • Prof. Mao Ye,

    1. State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology and College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (P.R. China)
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  • Dr. Liu Yang,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
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  • Dr. Kwame Sefah,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
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  • Dr. Meghan B. O'Donoghue,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
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  • Dr. Yan Chen,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
    2. State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology and College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (P.R. China)
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  • Xiangling Xiong,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
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  • Dr. Jin Huang,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
    2. State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology and College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (P.R. China)
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  • Prof. Erqun Song,

    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
    2. Key Laboratory of Luminescence and Real-Time Analysis of the Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715 (P.R. China)
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  • Prof. Weihong Tan

    Corresponding author
    1. Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410
    • Center for Research at the Bio/Nano Interface, Departments of Chemistry, Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200 (USA), Fax: (+1) 352-846-2410

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Abstract

Monovalent aptamers can deliver drugs to target cells by specific recognition. However, different cancer subtypes are distinguished by heterogeneous biomarkers and one single aptamer is unable to recognize all clinical samples from different patients with even the same type of cancers. To address heterogeneity among cancer subtypes for targeted drug delivery, as a model, we developed a drug carrier with a broader recognition range of cancer subtypes. This carrier, sgc8c-sgd5a (SD), was self-assembled from two modified monovalent aptamers. It showed bispecific recognition abilities to target cells in cell mixtures; thus broadening the recognition capabilities of its parent aptamers. The self-assembly of SD simultaneously formed multiple drug loading sites for the anticancer drug doxorubicin (Dox). The Dox-loaded SD (SD–Dox) also showed bispecific abilities for target cell binding and drug delivery. Most importantly, SD–Dox induced bispecific cytotoxicity in target cells in cell mixtures. Therefore, by broadening the otherwise limited recognition capabilities of monovalent aptamers, bispecific aptamer-based drug carriers would facilitate aptamer applications for clinically heterogeneous cancer subtypes that respond to the same cancer therapy.

Abstract

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