A designed 5-fluorouracil-based bridged silsesquioxane as an autonomous acid-triggered drug-delivery system.
Two new prodrugs, bearing two and three 5-fluorouracil (5-FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5-FU, they were intended to form complexes through H-bonds to an organo-bridged silane prior to hydrolysis-condensation through sol-gel processes to construct acid-responsive bridged silsesquioxanes (BS). Whereas 5-FU itself and the prodrug bearing two 5-FU units completely leached out from the corresponding materials, the prodrug bearing three 5-FU units was successfully maintained in the resulting BS. Solid-state NMR ((29) Si and (13) C) spectroscopy show that the organic fragments of the organo-bridged silane are retained in the hybrid through covalent bonding and the (1) H NMR spectroscopic analysis provides evidence for the hydrogen-bonding interactions between the prodrug bearing three 5-FU units and the triazine-based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and (13) C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5-FU thanks to a controlled and targeted drug delivery.
Laboratory Architectures Moléculaires et Matériaux Nanostructurés, Institut Charles Gerhardt Montpellier (UMR 5253 CNRS-UM2-ENSCM-UM1), ENSCM, 8 rue de l'école normale 34296 Montpellier (France).
Simon
S
Giret
Christophe
C
Théron
Audrey
A
Gallud
Marie
M
Maynadier
Magali
M
Gary-Bobo
Marcel
M
Garcia
Michel
M
Wong Chi Man
Carole
C
Carcel
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005472:Fluorouracil / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D061986:MCF-7 Cells; D017646:Organosilicon Compounds / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
D001952:Bridged-Ring Compounds; D004337:Drug Carriers; D017646:Organosilicon Compounds; D011355:Prodrugs; D005472:Fluorouracil
cancer; drug delivery; drug design; hydrogen bonding; sol-gel processes