Metal–Organic Polyhedron Capped with Cucurbit[8]uril Delivers Doxorubicin to Cancer Cells
| Autor: | Soumen K. Samanta, Lyle Isaacs, Damien Moncelet, Volker Briken |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Bridged-Ring Compounds
Models Molecular Stereochemistry Molecular Conformation 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis HeLa Metal chemistry.chemical_compound Colloid and Surface Chemistry Organometallic Compounds Humans Prodrugs Drug Carriers biology 010405 organic chemistry Chemistry Ligand Imidazoles General Chemistry Hydrogen-Ion Concentration Prodrug biology.organism_classification Fluorescence 0104 chemical sciences MOPS Doxorubicin Covalent bond visual_art Proton NMR visual_art.visual_art_medium HeLa Cells Nuclear chemistry |
| Zdroj: | Journal of the American Chemical Society. 138:14488-14496 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Self-assembly of ligand 1 and Pd(NO3)2 delivers Fujita-type metal organic polyhedron (MOP) 3 which bears 24 covalently attached methyl viologen units on its external surface as evidenced by 1H NMR, DOSY NMR, electrospray mass spectrometry, TEM, and AFM measurements. MOP 3 undergoes non-covalent complexation with cucurbit[n]urils to yield MOPs 4 – 6 with diameter ≈ 5–6 nm. MOP 5 can be fully loaded with doxorubicin 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 doxorubicin 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. |
| Databáze: | OpenAIRE |
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