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

doi:10.7150/thno.21342

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 journal › Article › peer-review

26 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 language	English (US)
Pages (from-to)	31-44
Number of pages	14
Journal	Theranostics
Volume	8
Issue number	1
DOIs	https://doi.org/10.7150/thno.21342
State	Published - 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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Liu, H., Mai, J., Shen, J., Wolfram, J., Li, Z., Zhang, G., Xu, R., Li, Y., Mu, C., Zu, Y., Li, X., Lokesh, G. L., Thiviyanathan, V., Volk, D. E., Gorenstein, D. G., Ferrari, M., Hu, Z., & Shen, H. (2018). A novel DNA aptamer for dual targeting of polymorphonuclear myeloid-derived suppressor cells and tumor cells. Theranostics, 8(1), 31-44. https://doi.org/10.7150/thno.21342

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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 = "Active targeting, DNA aptamer, Liposome, Myeloid-derived suppressor cells (MDSCs), Tumor microenvironment",

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

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year = "2018",

doi = "10.7150/thno.21342",

language = "English (US)",

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TY - JOUR

T1 - A novel DNA aptamer for dual targeting of polymorphonuclear myeloid-derived suppressor cells and tumor cells

AU - Liu, Haoran

AU - Mai, Junhua

AU - Shen, Jianliang

AU - Wolfram, Joy

AU - Li, Zhaoqi

AU - Zhang, Guodong

AU - Xu, Rong

AU - Li, Yan

AU - Mu, Chaofeng

AU - Zu, Youli

AU - Li, Xin

AU - Lokesh, Ganesh L.

AU - Thiviyanathan, Varatharasa

AU - Volk, David E.

AU - Gorenstein, David G.

AU - Ferrari, Mauro

AU - Hu, Zhongbo

AU - Shen, Haifa

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Active targeting

KW - DNA aptamer

KW - Liposome

KW - Myeloid-derived suppressor cells (MDSCs)

KW - Tumor microenvironment

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

Abstract

Keywords

ASJC Scopus subject areas

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