Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111941
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Type: Journal article
Title: Albumin binding domain fusing R/K-X-X-R/K sequence for enhancing tumor delivery of doxorubicin
Author: Liu, L.
Zhang, C.
Li, Z.
Wang, C.
Bi, J.
Yin, S.
Wang, Q.
Yu, R.
Liu, Y.
Su, Z.
Citation: Molecular Pharmaceutics, 2017; 14(11):3739-3749
Publisher: American Chemical Society
Issue Date: 2017
ISSN: 1543-8384
1543-8392
Statement of
Responsibility: 
Liping Liu, Chun Zhang, Zenglan Li, Chunyue Wang, Jingxiu Bi, Shuang Yin, Qi Wang, Rong Yu, Yongdong Liu and Zhiguo Su
Abstract: For the purpose of improving the tumor delivery of doxorubicin (DOX), a kind of peptide-DOXO conjugate was designed and prepared, in which the peptide composed of an albumin-binding domain (ABD) and a tumor-specific internalizing sequence (RGDK or RPARPAR) was conjugated to a (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH). The doxorubicin uptake by lung cancer cell line of A549 evidenced that the conjugates are capable of being internalized through a tumor-specific sequence mediated manner, and the intracellular imaging of distribution in A549 cell demonstrated that the conjugated doxorubicin can be delivered to the cell nucleus. The A549 cell cytotoxicity of peptide-DOXO conjugates was presented with IC50 values and shown in the range of about 9-11 μM. Pharmacokinetics study revealed that both conjugates exhibited nearly 5.5 times longer half-time than DOX, and about 4 times than DOXO-EMCH. The in vivo growth inhibitions of the two peptide-DOXO conjugates on BALB/c nude mice bearing A549 tumor (47.78% for ABD-RGDK-DOXO and 47.09% for ABD-RPARPAR-DOXO) were much stronger than that of doxorubicin and DOXO-EMCH (24.28% and 25.67% respectively) at a doxorubicin equivalent dose. Besides, the in vivo fluorescence imaging study confirmed that the peptide markedly increased the payload accumulation in tumor tissues and indicated that albumin binding domain fusing tumor-specific sequence effectively enhanced the tumor delivery of doxorubicin and thus improved its therapeutic potency.
Keywords: RGDK; RPARPAR; albumin binding domain; doxorubicin; peptide-drug conjugate
Rights: © 2017 American Chemical Society
RMID: 0030076510
DOI: 10.1021/acs.molpharmaceut.7b00497
Appears in Collections:Pharmacology publications

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