A novel DNA aptamer for dual targeting of polymorphonuclear myeloid-derived suppressor cells and tumor cells

Haoran Liu, Junhua Mai, Jianliang Shen, Joy Wolfram, Zhaoqi Li, Guodong Zhang, Rong Xu, Yan Li, Chaofeng Mu, Youli Zu, Xin Li, Ganesh L. Lokesh, Varatharasa Thiviyanathan, David E. Volk, David G. Gorenstein, Mauro Ferrari, Zhongbo Hu, Haifa Shen

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)31-44
Number of pages14
JournalTheranostics
Volume8
Issue number1
DOIs
StatePublished - 2018

Keywords

  • Active targeting
  • DNA aptamer
  • Liposome
  • Myeloid-derived suppressor cells (MDSCs)
  • Tumor microenvironment

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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