Cell-penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy

Jue Yeon Lee, Young Suk Choi, Jin Sook Suh, Young Min Kwon, Victor C. Yang, Seung Jin Lee, Chong Pyoung Chung, Yoon Jeong Park

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

In this study, a cell-penetrating peptide, the transactivating transcriptional factor (TAT) domain from HIV, was linked to a chitosan/doxorubicin (chitosan/DOX) conjugate to form a chitosan/DOX/TAT hybrid. The synthesized chitosan/DOX/TAT conjugate showed a different intracellular distribution pattern from a conjugate without TAT. Unlike both free DOX and the conjugate without TAT, the chitosan/DOX/TAT conjugate was capable of efficient cell entry. The chitosan/DOX/TAT conjugate was found to be highly cytotoxic, with an IC50 value of approximately 480 nM, 2 times less than that of chitosan/DOX (980 nM). The chitosan/DOX/TAT provided decreases in tumor volume of 77.4 and 57.5% compared to free DOX and chitosan/DOX, respectively, in tumor-bearing mice. Therefore, this study suggests that TAT-mediated chitosan/DOX conjugate delivery is effective in slowing tumor growth.

Original languageEnglish
Pages (from-to)2470-2480
Number of pages11
JournalInternational Journal of Cancer
Volume128
Issue number10
DOIs
StatePublished - 1 May 2011

Keywords

  • Cell-penetrating peptide
  • TAT
  • chitosan conjugate
  • doxorubicin
  • tumor

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