Cell-penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy.
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.
Lee
Jue-Yeon
JY
Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea.
Choi
Young-Suk
YS
Suh
Jin-Sook
JS
Kwon
Young-Min
YM
Yang
Victor C
VC
Lee
Seung-Jin
SJ
Chung
Chong-Pyoung
CP
Park
Yoon-Jeong
YJ
D000818:Animals; D048271:Chitosan / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014157:Transcription Factors / Q000627:therapeutic use*
D014157:Transcription Factors; D004317:Doxorubicin; D048271:Chitosan