期刊
THERANOSTICS
卷 8, 期 1, 页码 31-44出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.21342
关键词
DNA aptamer; active targeting; tumor microenvironment; myeloid-derived suppressor cells (MDSCs); liposome
资金
- National Institutes of Health [1R01CA193880-01A1, U54CA210181]
- U.S. Department of Defense [W81XWH-12-1-0414]
- Huazhong University of Science and Technology [2016YXZD035, 2017KFKJXX004]
- University of Chinese Academy of Sciences
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.
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