Enhanced targeted anticancer effects and inhibition of tumor metastasis by the TMTP1 compound peptide TMTP1-TAT-NBD

Journal of Controlled Release : Official Journal of the Controlled Release Society
Rong-hua LiuDing Ma

Abstract

Micromolecular agents that block tumor development and metastasis hold great promise as cancer-targeted therapies. Tumor molecular targeted peptide 1 (TMTP1) was previously shown to target primary tumors and metastatic foci specifically. In this study, a group of composite peptides were incorporated to TMPT1. The NF-κB essential modulator-binding domain (NBD), and the trans-activator of transcription (TAT) peptide, were synthesized to enhance the targeted anti-tumor effects of TMTP1. TMTP1-NBD did not exhibit strong affinity to tumor cells as we had expected. Conjugating TAT with TMTP1-NBD ameliorated the poor hydrophilicity and negative charge of TMTP1-NBD. Therefore TMTP1-TAT-NBD displayed strong affinity and anti-tumor effects as we expected in vivo and in vitro. Interestingly cytoplasmic glycogen accumulation as well as apoptosis was observed in TMTP1-TAT-NBD treated PC-3M-1E8 cells. The downstream signaling pathways including AKT, GSK-3β, IκBα and NF-κB activity were verified to decrease by TMTP1-TAT-NBD. The pharmacokinetics and distribution of TMTP1-TAT-NBD in MDA-MB-231 tumor-bearing mice model provided some evidence for safety of the composite peptide, which showed the fluorescence of the peptide peaked in the tumor 6h...Continue Reading

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Citations

Oct 26, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ronghua LiuLing Xi
May 20, 2014·Cancer Letters·Dongdong WuYanzhang Li
Jan 24, 2016·International Journal of Pharmaceutics·John W McBrideHelen O McCarthy
May 8, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gemma M RyanChristopher J H Porter
Feb 15, 2015·Nanomedicine : Nanotechnology, Biology, and Medicine·Ting LiuTianfeng Chen
Feb 1, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Antonella BorrelliFranco M Buonaguro
Aug 31, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiuxia YanYi Ma
Dec 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuanjun DengGang Xu
Mar 7, 2020·Pharmaceutics·Rebecca E Taylor, Maliha Zahid
Jun 29, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Amir Nasrolahi ShiraziKeykavous Parang
Nov 27, 2018·Bioconjugate Chemistry·Ying ZhouLing Xi
Aug 21, 2021·Advanced Healthcare Materials·Jun DaiShixuan Wang

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