title: Metal-Organic Polyhedron Capped with Cucurbit[8]uril Delivers Doxorubicin to Cancer Cells.
abstract: Self-assembly of ligand 1 and Pd(NO3)2delivers Fujita-type metal-organic polyhedron (MOP) 3 which bears 24 covalently attached methyl viologen units on its external surface, as evidenced by1H NMR, diffusion-ordered spectroscopy NMR, electrospray mass spectrometry, transmission electron microscopy, and atomic force microscopy measurements. MOP 3 undergoes noncovalent complexation with cucurbit[n]urils to yield MOPs 4-6 with diameter ≈5-6 nm. MOP 5 can be fully loaded with doxorubicin (DOX) prodrug 2 via hetero-ternary complex formation to yield 7. The MOPs exhibit excellent stability toward neutral to slightly acidic pH in 10 mM sodium phosphate buffer, mitigating the concern of disassembly during circulation. The results of MTS assays show that MOP 7 is 10-fold more cytotoxic toward HeLa cells than equimolar quantities of DOX prodrug 2. The enhanced cytotoxicity can be traced to a combination of enhanced cellular uptake of 7 and DOX release as demonstrated by flow cytometry and confocal fluorescence microscopy. The confluence of properties imparted by the polycationic MOP architecture and plug-and-play CB[n] complexation provides a potent new platform for drug delivery application.
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Soumen K
authors.initials: SK
authors.lastname: Samanta
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Damien
authors.initials: D
authors.lastname: Moncelet
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Volker
authors.initials: V
authors.lastname: Briken
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Lyle
authors.initials: L
authors.lastname: Isaacs
mesh_terms: D001952:Bridged-Ring Compounds / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D011355:Prodrugs / Q000378:metabolism; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D001952:Bridged-Ring Compounds; D004317:Doxorubicin; D004337:Drug Carriers; D007093:Imidazoles; D009942:Organometallic Compounds; D011355:Prodrugs; C507198:cucurbit(8)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils