PEGylated TNF-related apoptosis-inducing ligand (TRAIL) analogues: Pharmacokinetics and antitumor effects

Tae Hyung Kim, Yu Seok Youn, Hai Hua Jiang, Seulki Lee, Xiaoyuan Chen, Kang Choon Lee

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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 Mw might be useful antitumor agent with protracted activity.

Original languageEnglish (US)
Pages (from-to)1631-1637
Number of pages7
JournalBioconjugate Chemistry
Issue number8
StatePublished - Aug 17 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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