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

Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures. In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through selection and validation in breast cancer models. The use of T1 as a target...

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Bibliographic Details
Published in:Theranostics 2018, Vol.8 (1), p.31-44
Main Authors: Liu, Haoran, Mai, Junhua, Shen, Jianliang, Wolfram, Joy, Li, Zhaoqi, Zhang, Guodong, Xu, Rong, Li, Yan, Mu, Chaofeng, Zu, Youli, Li, Xin, Lokesh, Ganesh L, Thiviyanathan, Varatharasa, Volk, David E, Gorenstein, David G, Ferrari, Mauro, Hu, Zhongbo, Shen, Haifa
Format: Article
Language:English
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Research Paper
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Summary:Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures. In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through selection and validation in breast cancer models. The use of T1 as a targeting ligand was evaluated by conjugating the aptamer to liposomal doxorubicin. 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. 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.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.21342