A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

被引：31

作者：

Fadzen, Colin M. ^{[1
]}

Wolfe, Justin M. ^{[1
]}

Zhou, Wen ^{[1
,2
]}

Cho, Choi-Fong ^{[3
]}

von Spreckelsen, Niklas ^{[3
,4
,5
]}

Hutchinson, Kathryn T. ^{[3
]}

Lee, Yen-Chun ^{[1
]}

Chiocca, E. Antonio ^{[3
]}

Lawler, Sean E. ^{[3
]}

Yilmaz, Omer H. ^{[2
]}

Lippard, Stephen J. ^{[1
]}

Pentelute, Bradley L. ^{[1
,2
]}

机构：

[1] MIT, Dept Chem, Cambridge, MA 02139 USA

[2] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Harvey Cushing Neurooncol Labs, Dept Neurosurg, Boston, MA 02115 USA

[4] Univ Cologne, Fac Med, Dept Neurosurg, Ctr Neurosurg, D-50937 Cologne, Germany

[5] Univ Cologne, Univ Hosp, D-50937 Cologne, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 63卷 / 13期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

TRANSITION-METAL-COMPLEXES; DRUG DESIGN; PHASE-II; IN-VITRO; CISPLATIN; CARBOPLATIN; GLIOMA; TUMOR; PHARMACOKINETICS; CELLS;

D O I：

10.1021/acs.jmedchem.0c00022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate shows efficacy against glioma stem-like cells. We investigate the pharmacokinetics of this conjugate in mice and show that the amount of platinum in the brain after treatment with the conjugate is 15-fold greater than with cisplatin after 5 h.

引用

收藏

页码：6741 / 6747

页数：7

相关论文

共 33 条

[1] Solid-phase synthesis of oxaliplatin-TAT peptide bioconjugates [J].

Abramkin, Sergey ;

Valiahdi, Seied M. ;

Jakupec, Michael A. ;

Galanski, Markus ;

Metzler-Nolte, Nils ;

Keppler, Bernhard K. .

DALTON TRANSACTIONS, 2012, 41 (10) :3001-3005

[2] Lighting the way to see inside the live cell with luminescent transition metal complexes [J].

Baggaley, Elizabeth ;

Weinstein, Julia A. ;

Williams, J. A. Gareth .

COORDINATION CHEMISTRY REVIEWS, 2012, 256 (15-16) :1762-1785

[3] Anticancer activity of osmium(VI) nitrido complexes in patient-derived glioblastoma initiating cells and in vivo mouse models [J].

Berger, Gilles ;

Grauwet, Korneel ;

Zhang, Hong ;

Hussey, Amanda M. ;

Nowicki, Michal O. ;

Wang, David I. ;

Chiocca, E. Antonio ;

Lawler, Sean E. ;

Lippard, Stephen J. .

CANCER LETTERS, 2018, 416 :138-148

[4] FORMATION OF DNA-ADDUCTS BY THE ANTICANCER DRUG CARBOPLATIN - DIFFERENT NUCLEOTIDE-SEQUENCE PREFERENCES IN-VITRO AND IN CELLS [J].

BLOMMAERT, FA ;

VANDIJKKNIJNENBURG, HCM ;

DIJT, FJ ;

DENENGELSE, L ;

BAAN, RA ;

BERENDS, F ;

FICHTINGERSCHEPMAN, AMJ .

BIOCHEMISTRY, 1995, 34 (26) :8474-8480

[5] THE MECHANISM OF RENAL CLEARANCE OF CISPLATIN (CIS-DICHLORODIAMMINE PLATINUM-II) AND ITS MODIFICATION BY FUROSEMIDE AND PROBENECID [J].

DALEYYATES, PT ;

MCBRIEN, DCH .

BIOCHEMICAL PHARMACOLOGY, 1982, 31 (13) :2243-2246

[6] Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles [J].

Dhar, Shanta ;

Gu, Frank X. ;

Langer, Robert ;

Farokhzad, Omid C. ;

Lippard, Stephen J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (45) :17356-17361

[7] Pharmacokinetics of cisplatin and relation to nephrotoxicity in paediatric patients [J].

Erdlenbruch, B ;

Nier, M ;

Kern, W ;

Hiddemann, W ;

Pekrun, A ;

Lakomek, M .

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2001, 57 (05) :393-402

[8] Perfluoroarene-Based Peptide Macrocycles to Enhance Penetration Across the Blood-Brain Barrier [J].

Fadzen, Colin M. ;

Wolfe, Justin M. ;

Cho, Choi-Fong ;

Chiocca, E. Antonio ;

Lawler, Sean E. ;

Pentelute, Bradley L. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2017, 139 (44) :15628-15631

[9] Synthesis and in vitro cytotoxicity of cis,cis,trans-diamminedichloridodisuccinatoplatinum(IV)-peptide bioconjugates [J].

Gaviglio, Luca ;

Gross, Annika ;

Metzler-Nolte, Nils ;

Ravera, Mauro .

METALLOMICS, 2012, 4 (03) :260-266

[10]

Johnstone T. C., 2014, J BIOL INORG CHEM, V19, P674

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