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

被引：49

作者：

Liu, Haoran ^{[1
,2
]}

Mai, Junhua ^{[2
]}

Shen, Jianliang ^{[2
]}

Wolfram, Joy ^{[2
,3
]}

Li, Zhaoqi ^{[2
,4
]}

Zhang, Guodong ^{[2
]}

Xu, Rong ^{[5
]}

Li, Yan ^{[2
]}

Mu, Chaofeng ^{[2
]}

Zu, Youli ^{[6
]}

Li, Xin ^{[7
,8
]}

Lokesh, Ganesh L. ^{[7
,8
]}

Thiviyanathan, Varatharasa ^{[7
,8
]}

Volk, David E. ^{[7
,8
]}

Gorenstein, David G. ^{[7
,8
]}

Ferrari, Mauro ^{[2
,9
]}

Hu, Zhongbo ^{[1
]}

Shen, Haifa ^{[2
,10
]}

机构：

[1] Univ Chinese Acad Sci, Coll Mat Sci & Optoelect Technol, Beijing 100049, Peoples R China

[2] Houston Methodist Hosp, Dept Nanomed, Res Inst, Houston, TX 77030 USA

[3] Mayo Clin, Dept Transplantat, Jacksonville, FL 32224 USA

[4] Cent South Univ, Xiangya Hosp, Changsha 410013, Hunan, Peoples R China

[5] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pharmacol, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China

[6] Houston Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA

[7] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, McGovern Med Sch, Houston, TX 77030 USA

[8] Univ Texas Hlth Sci Ctr Houston, Dept Nanomed & Biomed Engn, McGovern Med Sch, Houston, TX 77030 USA

[9] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[10] Weill Cornell Med, Dept Cell & Dev Biol, New York, NY 10065 USA

来源：

THERANOSTICS | 2018年 / 8卷 / 01期

基金：

美国国家卫生研究院;

关键词：

DNA aptamer; active targeting; tumor microenvironment; myeloid-derived suppressor cells (MDSCs); liposome; CHECKPOINT BLOCKADE; DRUG-DELIVERY; THERAPEUTICS; NANOPARTICLES; CHEMOTHERAPY; GENERATION; RESISTANCE; LIPOSOMES; SELECTION; DESIGN;

D O I：

10.7150/thno.21342

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：31 / 44

页数：14

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