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

doi:10.1002/ijc.25578

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

66 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 language	English
Pages (from-to)	2470-2480
Number of pages	11
Journal	International Journal of Cancer
Volume	128
Issue number	10
DOIs	https://doi.org/10.1002/ijc.25578
State	Published - 1 May 2011

Keywords

Cell-penetrating peptide
TAT
chitosan conjugate
doxorubicin
tumor

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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 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.",

keywords = "Cell-penetrating peptide, TAT, chitosan conjugate, doxorubicin, tumor",

author = "Lee, {Jue Yeon} and Choi, {Young Suk} and Suh, {Jin Sook} and Kwon, {Young Min} and Yang, {Victor C.} and Lee, {Seung Jin} and Chung, {Chong Pyoung} and Park, {Yoon Jeong}",

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AU - Lee, Jue Yeon

AU - Choi, Young Suk

AU - Suh, Jin Sook

AU - Kwon, Young Min

AU - Yang, Victor C.

AU - Lee, Seung Jin

AU - Chung, Chong Pyoung

AU - Park, Yoon Jeong

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

KW - Cell-penetrating peptide

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KW - chitosan conjugate

KW - doxorubicin

KW - tumor

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JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 10

ER -

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

Abstract

Keywords

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