E-selectin Targeting PEGylated-thioaptamer Prevents Breast Cancer Metastases

Yoshihiro Morita(University of Oklahoma Health Sciences Center), Mohamed Kamal(University of Oklahoma Health Sciences Center), Shinae Kang(University of Oklahoma Health Sciences Center), Roy Zhang(University of Oklahoma Health Sciences Center), G.L. Lokesh(The University of Texas Health Science Center at Houston), Varatharasa Thiviyanathan(The University of Texas Health Science Center at Houston), Nafis Hasan(Thomas Jefferson University), Sukyung Woo(University of Oklahoma Health Sciences Center), Daniel Zhao(University of Oklahoma Health Sciences Center), Macall Leslie(University of Oklahoma Health Sciences Center), Stephen Suh(Hackensack University Medical Center), Wajeeha Razaq(University of Oklahoma Health Sciences Center), Hallgeir Rui(Medical College of Wisconsin), David G. Gorenstein(Raptamer Discovery Group (United States)), David E. Volk(The University of Texas Health Science Center at Houston), Takemi Tanaka(University of Oklahoma Health Sciences Center)
Molecular Therapy — Nucleic Acids
January 1, 2016
10.1038/mtna.2016.103
Cited by 31Open Access
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Abstract

BCa to E-selectin-expressing human endothelial cells (HMVECs) at a level equal to ESTA. Chemical conjugation of methoxy-polyethylene-glycol (PEG) at the sizes of 5 and 10 kDa did not interfere with ESTA7-mediated shear-resistant adhesion. However, in vivo study demonstrated that only 10 kDa PEG-conjugated ESTA7 (ESTA7-p10) retains the activity to inhibit metastases at a level equal to parental ESTA. Additionally, a single intravenous injection of ESTA7-p10 inhibited the development of lung, brain, and bone metastases of MDA-MB-231, through the blockade of E-selectin. Moreover, PEGylation led to an extension of elimination half-life and increase of AUC, resulting in superior inhibition of metastasis development compared to parental ESTA with a longer interval between dosing in a spontaneous metastasis model. Lastly, repeated intravenous administration of ESTA7-p10 was tolerated in mice, highlighting the potential prophylactic application of ESTA7-p10 for metastasis prevention.

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