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Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin
Liu, Liping1,2; Zhang, Chun1,2; Li, Zenglan2; Wang, Chunyue1,2; Bi, Jingxiu3; Yin, Shuang1,2,3; Wang, Qi2; Yu, Rong1; Liu, Yongdong2; Su, Zhiguo2
2017-11-01
Source PublicationMOLECULAR PHARMACEUTICS
ISSN1543-8384
Volume14Issue:11Pages:3739-3749
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 mu M. 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.

KeywordAlbumin Binding Domain Rgdk Rparpar Doxorubicin Peptide-drug Conjugate
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1021/acs.molpharmaceut.7b00497
Indexed BySCI
Language英语
WOS KeywordPeptide-conjugated Doxorubicin ; Antitumor Efficacy ; Drug-resistance ; Breast-cancer ; Serum-albumin ; Cardiotoxicity ; Release ; Carrier ; Cells ; Platform
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
Funding OrganizationNational Natural Science Foundation of China(21576267) ; Beijing Natural Science Foundation(2162041) ; National Key Laboratory of Biochemical Engineering(2014KF-05) ; Major State Basic Research Development Program of China(2013CB733604)
WOS IDWOS:000414820000012
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/23386
Collection生化工程国家重点实验室
Affiliation1.Sichuan Univ, West China Sch Pharm, Minist Educ, Key Lab Drug Targeting & Drug Delivery Syst, Chengdu 610041, Sichuan, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
3.Univ Adelaide, Sch Chem Engn, Adelaide, SA 5005, Australia
Recommended Citation
GB/T 7714
Liu, Liping,Zhang, Chun,Li, Zenglan,et al. Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin[J]. MOLECULAR PHARMACEUTICS,2017,14(11):3739-3749.
APA Liu, Liping.,Zhang, Chun.,Li, Zenglan.,Wang, Chunyue.,Bi, Jingxiu.,...&Su, Zhiguo.(2017).Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin.MOLECULAR PHARMACEUTICS,14(11),3739-3749.
MLA Liu, Liping,et al."Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin".MOLECULAR PHARMACEUTICS 14.11(2017):3739-3749.
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