Theranostics 2018; 8(1):31-44. doi:10.7150/thno.21342

Research Paper

A Novel DNA Aptamer for Dual Targeting of Polymorphonuclear Myeloid-derived Suppressor Cells and Tumor Cells

Haoran Liu1,2, Junhua Mai2, Jianliang Shen2, Joy Wolfram2,3, Zhaoqi Li2,4, Guodong Zhang2, Rong Xu5, Yan Li2, Chaofeng Mu2, Youli Zu6, Xin Li7, Ganesh L. Lokesh7, Varatharasa Thiviyanathan7, David E. Volk7, David G. Gorenstein7, Mauro Ferrari2,8, Zhongbo Hu1, Haifa Shen2,9✉

1. College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China
2. Department of Nanomedicine, Houston Methodist Hospital Research Institute, Houston, TX 77030, USA
3. Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA
4. Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
5. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
6. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA
7. Institute of Molecular Medicine and the Department of Nanomedicine and Biomedical Engineering, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77030, USA
8. Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
9. Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065, USA

Abstract

Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures.

Methods: In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through in vivo selection and validation in breast cancer models. The use of T1 as a targeting ligand was evaluated by conjugating the aptamer to liposomal doxorubicin.

Results: T1 exhibited a high affinity for both tumor cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Treatment with T1 targeted doxorubicin liposomes triggered apoptosis of breast cancer cells and PMN-MDSCs. Suppression of PMN-MDSCs, which serve an immunosuppressive function, leads to increased intratumoral infiltration of cytotoxic T cells. Conclusion: The cytotoxic and immunomodulatory effects of T1-liposomes resulted in superior therapeutic efficacy compared to treatment with untargeted liposomes, highlighting the promise of T1 as a targeting ligand in cancer therapy.

Keywords: DNA aptamer, active targeting, tumor microenvironment, myeloid-derived suppressor cells (MDSCs), liposome

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How to cite this article:
Liu H, Mai J, Shen J, Wolfram J, Li Z, Zhang G, Xu R, Li Y, Mu C, Zu Y, Li X, Lokesh GL, Thiviyanathan V, Volk DE, Gorenstein DG, Ferrari M, Hu Z, Shen H. A Novel DNA Aptamer for Dual Targeting of Polymorphonuclear Myeloid-derived Suppressor Cells and Tumor Cells. Theranostics 2018; 8(1):31-44. doi:10.7150/thno.21342. Available from http://www.thno.org/v08p0031.htm