Synthesis and characterization of CD133 targeted aptamer–drug conjugates for precision therapy of anaplastic thyroid cancer

Authors:
Publisher website
Google Scholar
Abstract
Anaplastic thyroid cancer (ATC) is an undifferentiated and highly aggressive type of thyroid cancer and is extremely resistant to standard therapies such as surgical resection and radioactive iodine therapy. Although targeted therapeutic agents including small molecule drugs and monoclonal antibodies are rapidly developed in recent years, no ATC targeted drugs are available to date; thereby, novel targeted therapies are needed to improve the outcomes of ATC patients. Aptamers are single-stranded DNA (or RNA) molecules that can selectively bind to cancer specific antigens, and aptamer-based targeted therapy has certain advantages over that based on antibodies due to its high binding affinity and low immunogenicity. Here, we identified that CD133, a cancer stem cell marker, was specifically expressed in ATC tumor tissues and cells, implying that CD133 is a potential drug target for ATC therapy. Additionally, we successfully obtained a CD133 targeted aptamer AP-1 by paired cell-based SELEX, which can precisely recognize CD133 antigen in vitro. Furthermore, the truncated AP-1-M aptamer from its precursor AP-1 has shown higher binding affinity for CD133, and specifically accumulated in anaplastic thyroid cancer FRO cell derived tumor in vivo. Conjugation of truncated AP-1-M with doxorubicin could dramatically inhibit CD133 positive FRO cell proliferation, induce cell apoptosis in vitro, and also suppress tumor growth in FRO cell xenograft mice in vivo. Our results clearly demonstrated that the CD133 targeted aptamer AP-1-M conjugated with anticancer drugs has potential to become a promising therapeutic approach against ATC in the near future.
Funding Information
  • National Science and Technology Major Project (2018ZX10302-206)
  • National Natural Science Foundation of China (81673521, 81672642, 81872942, 81872170)
  • China Postdoctoral Science Foundation (2020M681901)
  • Medical Science and Technology Project of Zhejiang Province (2020PY002)
  • Science and Technology Department of Zhejiang Province (LGF21H160007)
  • Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents

This publication has 50 references indexed in Scilit: