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

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

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 IC 50 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.

Publisher: Wiley Subscription Services, Inc., A Wiley Company
Year: 2011
DOI identifier: 10.1002/ijc.25578
OAI identifier: oai:deepblue.lib.umich.edu:2027.42/83474
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