title: Cell-penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy.
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.
authors.affiliation: Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Jue-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Choi
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Suh
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kwon
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chong-Pyoung
authors.initials: CP
authors.lastname: Chung
authors.forename: Yoon-Jeong
authors.initials: YJ
authors.lastname: Park
mesh_terms: 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*
chemical_list: D014157:Transcription Factors; D004317:Doxorubicin; D048271:Chitosan