Journal
BIOCONJUGATE CHEMISTRY
Volume 22, Issue 8, Pages 1631-1637Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc200187k
Keywords
-
Categories
Funding
- Korean Ministry of Education, Science, and Technology [2010K001256]
Ask authors/readers for more resources
The low stability and fast clearance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are the main obstacles to its implementation as an antitumor agent. Here, we attempted to improve its pharmacokinetic and pharmacodynamic profiles by using PEGylation. N-terminal PEGylated TRAIL (PEG-TRAIL) was synthesized using 2, 5, 10, 20, and 30 kDa PEG. Antitumor effect assessments in HCT116 tumor bearing nude mice showed that all PEG-TRAIL analogues efficiently suppressed mean tumor growth, with mean tumor growth inhibition (TGI) values (5K-, 20K-, 30K-PEG-TRAIL) of 43.5, 61.7, and 72.3%, respectively. In particular, 30K-PEG-TRAIL was found to have antitumor efficacy for five days after a single administration (1 mg/mouse, ip). The different antitumor effects of these PEG-TRAIL analogues were attributed to augmented pharmacokinetics and metabolic resistance. All analogues were found to have higher metabolic stabilities in rat plasma, extended pharmacokinetic profiles, and greater circulating half-lives (3.9, 5.3, 6.2, 12.3, and 17.7 h for 2, 5, 10, 20, and 30K-PEG-TRAIL, respectively, versus 1.1 h for TRAIL, ip) in ICR mice. Our findings suggest that TRAIL derivatized with PEG of an appropriate M(w) might be useful antitumor agent with protracted activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available