Bioconjugation of Supramolecular Metallacages to Integrin Ligands for Targeted Delivery of Cisplatin

被引：49

作者：

Han, Jiaying ^{[1
]}

Raeder, Andreas F. B. ^{[2
,3
]}

Reichart, Florian ^{[2
,3
]}

Aikman, Brech ^{[4
]}

Wenzel, Margot N. ^{[4
]}

Woods, Ben ^{[4
]}

Weinmueller, Michael ^{[2
,3
]}

Ludwig, Beatrice S. ^{[2
,3
]}

Sturup, Stefan ^{[5
]}

Groothuis, Geny M. M. ^{[1
]}

Permentier, Hjalmar P. ^{[1
]}

Bischoff, Rainer ^{[1
]}

Kessler, Horst ^{[2
,3
]}

Horvatovich, Peter ^{[1
]}

Casini, Angela ^{[4
]}

机构：

[1] Univ Groningen, Groningen Res Inst Pharm, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands

[2] Tech Univ Munich, Inst Adv Study, Dept Chem, Lichtenbergstr 4, D-85747 Garching, Germany

[3] Tech Univ Munich, Dept Chem, CIPSM, Lichtenbergstr 4, D-85747 Garching, Germany

[4] Cardiff Univ, Sch Chem, Main Bldg,Pk Pl, Cardiff CF10 3AT, S Glam, Wales

[5] Univ Copenhagen, Dept Pharm, Univ Pk 2, DK-2100 Copenhagen, Denmark

来源：

BIOCONJUGATE CHEMISTRY | 2018年 / 29卷 / 11期

基金：

欧盟第七框架计划;

关键词：

CYCLIC RGD PEPTIDES; COORDINATION-COMPLEXES; TRANSPORT MECHANISMS; SELECTIVE LIGANDS; PALLADIUM CAGES; RATIONAL DESIGN; IN-VITRO; ALPHA-5-BETA-1; ALPHA-V-BETA-3; PENTAPEPTIDES;

D O I：

10.1021/acs.bioconjchem.8b00682

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Cisplatin occupies a crucial role in the treatment of various malignant tumors. However, its efficacy and applicability are heavily restricted by severe systemic toxicities and drug resistance. Our study exploits the active targeting of supramolecular metallacages to enhance the activity of cisplatin in cancer cells while reducing its toxicity. Thus, Pd2L4 cages (L = ligand) have been conjugated to four integrin ligands with different binding affinity and selectivity. Cage formation and encapsulation of cisplatin was proven by NMR spectroscopy. Upon encapsulation, cisplatin showed increased cytotoxicity in vitro, in melanoma A375 cells overexpressing alpha v beta 3 integrins. Moreover, ex vivo studies in tissue slices indicated reduced toxicity toward healthy liver and kidney tissues for cage-encapsulated cisplatin. Analysis of metal content by ICP-MS demonstrated that the encapsulated drug is less accumulated in these organs compared to the "free" cisplatin.

引用

页码：3856 / 3865

页数：10

共 53 条

[1] Anticancer Potencies of PtII- and PdII-linked M2L4 Coordination Capsules with Improved Selectivity [J].

Ahmedova, Anife ;

Momekova, Denitsa ;

Yamashina, Masahiro ;

Shestakova, Pavletta ;

Momekov, Georgi ;

Akita, Munetaka ;

Yoshizawa, Michito .

CHEMISTRY-AN ASIAN JOURNAL, 2016, 11 (04) :474-477

[2] Nonconventional trans-Platinum Complexes Functionalized with RDG Peptides: Chemical and Cytototoxicity Studies [J].

Angeles Medrano, Maria ;

Morais, Mauricio ;

Ferreira, Vera F. C. ;

Correia, Joao D. G. ;

Paulo, Antonio ;

Santos, Isabel ;

Navarro-Ranninger, Carmen ;

Alvarez Valdes, Amparo ;

Casini, Angela ;

Mendes, Filipa ;

Quiroga, Adoracion G. .

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, 2017, (12) :1835-1840

[3] ARG-GLY-ASP CONSTRAINED WITHIN CYCLIC PENTAPEPTIDES - STRONG AND SELECTIVE INHIBITORS OF CELL-ADHESION TO VITRONECTIN AND LAMININ FRAGMENT-P1 [J].

AUMAILLEY, M ;

GURRATH, M ;

MULLER, G ;

CALVETE, J ;

TIMPL, R ;

KESSLER, H .

FEBS LETTERS, 1991, 291 (01) :50-54

[4] Caffeine-Based Gold(I) N-Heterocyclic Carbenes as Possible Anticancer Agents: Synthesis and Biological Properties [J].

Bertrand, Benoit ;

Stefan, Loic ;

Pirrotta, Marc ;

Monchaud, David ;

Bodio, Ewen ;

Richard, Philippe ;

Le Gendre, Pierre ;

Warmerdam, Elena ;

de Jager, Marina H. ;

Groothuis, Geny M. M. ;

Picquet, Michel ;

Casini, Angela .

INORGANIC CHEMISTRY, 2014, 53 (04) :2296-2303

[5] Drug transporters of platinum-based anticancer agents and their clinical significance [J].

Burger, Herman ;

Loos, Walter J. ;

Eechoute, Karel ;

Verweij, Jaap ;

Mathijssen, Ron H. J. ;

Wiemer, Erik A. C. .

DRUG RESISTANCE UPDATES, 2011, 14 (01) :22-34

[6] The Promise of Self-Assembled 3D Supramolecular Coordination Complexes for Biomedical Applications [J].

Casini, Angela ;

Woods, Benjamin ;

Wenzel, Margot .

INORGANIC CHEMISTRY, 2017, 56 (24) :14715-14729

[7] Biomedical and Biochemical Applications of Self-Assembled Metallacycles and Metallacages [J].

Cook, Timothy R. ;

Vajpayee, Vaishali ;

Lee, Min Hyung ;

Stang, Peter J. ;

Chi, Ki-Whan .

ACCOUNTS OF CHEMICAL RESEARCH, 2013, 46 (11) :2464-2474

[8] Metal-Organic Frameworks and Self-Assembled Supramolecular Coordination Complexes: Comparing and Contrasting the Design, Synthesis, and Functionality of Metal-Organic Materials [J].

Cook, Timothy R. ;

Zheng, Yao-Rong ;

Stang, Peter J. .

CHEMICAL REVIEWS, 2013, 113 (01) :734-777

[9] Improved Synthesis of N-Benzylaminoferrocene-Based Prodrugs and Evaluation of Their Toxicity and Antileukemic Activity [J].

Daum, Steffen ;

Chekhun, Vasiliy F. ;

Todor, Igor N. ;

Lukianova, Natalia Yu ;

Shvets, Yulia V. ;

Sellner, Leopold ;

Putzker, Kerstin ;

Lewis, Joe ;

Zenz, Thorsten ;

de Graaf, Inge A. M. ;

Groothuis, Geny M. M. ;

Casini, Angela ;

Zozulia, Oleksii ;

Hampel, Frank ;

Mokhir, Andriy .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (04) :2015-2024

[10] Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies [J].

de Graaf, Inge A. M. ;

Olinga, Peter ;

de Jager, Marina H. ;

Merema, Marjolijn T. ;

de Kanter, Ruben ;

van de Kerkhof, Esther G. ;

Groothuis, Geny M. M. .

NATURE PROTOCOLS, 2010, 5 (09) :1540-1551

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