Open Access
Open access
volume 5 issue 1 publication number 14872

Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities

Li Qiang Pan 1
Wen-Bin Zhao 1
JUN LAI 1
Xiao Yue Wei 1
Yang-Yang Li 1
Wen-Hui Liu 1
Xiao-Yue Yang 1
Ying-Chun Xu 1
Shu-qing Chen 1
Publication typeJournal Article
Publication date2015-10-08
scimago Q1
wos Q1
SJR0.874
CiteScore6.7
Impact factor3.9
ISSN20452322
PubMed ID:  26445897
Multidisciplinary
Abstract
Poor pharmacokinetics and resistance within some tumor cell lines have been the major obstacles during the preclinical or clinical application of TRAIL (tumor-necrosis-factor (TNF)-related apoptosis-inducing ligand). The half-life of TRAIL114-281 (114 to 281 amino acids) was revealed to be no more than 30 minutes across species. Therefore maleimido activated PEG (polyethylene glycol) and MMAE (Monomethyl Auristatin E) were applied to site-specifically conjugate with the mutated cysteines from different monomers of TRAIL successively, taking advantage of steric effects involved within TRAIL mutant conjugations. As a result, TRAIL trimer was hetero-modified for different purposes. And the resulting PEG-TRAIL-vcMMAE conjugate exhibited dramatically improved half-life (11.54 h), favourable in vivo targeting capability and antitumor activities while no sign of toxicity in xenograft models, suggesting it’s a viable therapeutic and drug delivery strategy.
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GOST Copy
Pan L. Q. et al. Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities // Scientific Reports. 2015. Vol. 5. No. 1. 14872
GOST all authors (up to 50) Copy
Pan L. Q., Zhao W., LAI J., Wei X. Y., Li Y., Liu W., Yang X., Xu Y., Chen S. Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities // Scientific Reports. 2015. Vol. 5. No. 1. 14872
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RIS Copy
TY - JOUR
DO - 10.1038/srep14872
UR - https://doi.org/10.1038/srep14872
TI - Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities
T2 - Scientific Reports
AU - Pan, Li Qiang
AU - Zhao, Wen-Bin
AU - LAI, JUN
AU - Wei, Xiao Yue
AU - Li, Yang-Yang
AU - Liu, Wen-Hui
AU - Yang, Xiao-Yue
AU - Xu, Ying-Chun
AU - Chen, Shu-qing
PY - 2015
DA - 2015/10/08
PB - Springer Nature
IS - 1
VL - 5
PMID - 26445897
SN - 2045-2322
ER -
BibTex
Cite this
BibTex (up to 50 authors) Copy
@article{2015_Pan,
author = {Li Qiang Pan and Wen-Bin Zhao and JUN LAI and Xiao Yue Wei and Yang-Yang Li and Wen-Hui Liu and Xiao-Yue Yang and Ying-Chun Xu and Shu-qing Chen},
title = {Hetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities},
journal = {Scientific Reports},
year = {2015},
volume = {5},
publisher = {Springer Nature},
month = {oct},
url = {https://doi.org/10.1038/srep14872},
number = {1},
pages = {14872},
doi = {10.1038/srep14872}
}