PEG-transferrin conjugated TRAIL (TNF-related apoptosis-inducing ligand) for therapeutic tumor targeting

Tae Hyung Kim, Young Gi Jo, Hai Hua Jiang, Sung Mook Lim, Yu Seok Youn, Seulki Lee, Xiaoyuan Chen, Youngro Byun, Kang Choon Lee

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Transferrin (Tf) is considered an effective tumor-targeting agent, and PEGylation effectively prolongs in vivo pharmacokinetics by delaying excretion via the renal route. The authors describe the active tumor targeting of long-acting Tf-PEG-TNF-related apoptosis-inducing ligand conjugate (Tf-PEG-TRAIL) for effective cancer therapy. Tf-PEG-TRAIL was prepared using a two-step N-terminal specific PEGylation procedure using different PEGs (Mw: 3.4, 5, 10 kDa). Eventually, only 10 kDa PEG was linked to Tf and TRAIL because TRAIL (66 kDa) and Tf (81 kDa) were too large to link to 3.4 and 5 kDa PEG. The final conjugate Tf-PEG10K-TRAIL was successfully purified and characterized by SDS-PAGE, western blotting. To determine the specific binding of Tf-PEG10K-TRAIL to Tf receptor, competitive receptor binding assays were performed on K 562 cells. The results obtained demonstrate that the affinity of Tf-PEG10K-TRAIL for Tf receptor is similar to that of native Tf. In contrast, PEG10K-TRAIL demonstrated no specificity. Biodistribution patterns and antitumor effects were investigated in C57BL6 mice bearing B16F10 murine melanomas and BALB/c athymic mice bearing HCT116. Tumor accumulation of Tf-PEG10K-TRAIL was 5.2 fold higher (at 2 h) than TRAIL, because Tf-PEG10K-TRAIL has both passive and active tumor targeting ability. Furthermore, the suppression of tumors by Tf-PEG 10K-TRAIL was 3.6 and 1.5 fold those of TRAIL and PEG 10K-TRAIL, respectively. These results suggest that Tf-PEG 10K-TRAIL is a superior pharmacokinetic conjugate that potently targets tumors and that it should be viewed as a potential cancer therapy.

Original languageEnglish (US)
Pages (from-to)422-428
Number of pages7
JournalJournal of Controlled Release
Issue number2
StatePublished - Sep 10 2012
Externally publishedYes


  • Active tumor targeting
  • PEGylation
  • Passive tumor targeting
  • Transferrin

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'PEG-transferrin conjugated TRAIL (TNF-related apoptosis-inducing ligand) for therapeutic tumor targeting'. Together they form a unique fingerprint.

Cite this