Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles.
MCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzymes, a zero release system was obtained. S1 was prepared by loading nanoparticles with Safranine O dye and was then capped with a gluconamide derivative. In the absence of enzymes, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase and pronase enzymes, delivery of Safranine O dye was observed due to the enzymatic hydrolysis of the amide bond in the anchored gluconamide derivative. S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays using HeLa and MCF-7 cell lines, and were associated with lysosomes, as shown by confocal microscopy. Finally, the S1–CPT material loaded with the cytotoxic drug camptothecin and capped with the gluconamide derivative was prepared. The HeLa cells treated with S1–CPT underwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo.
Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Unidad Mixta Universitat Politècnica de València-Universitat de València, Spain.
Inmaculada
I
Candel
Elena
E
Aznar
Laura
L
Mondragón
Cristina
C
de la Torre
Ramón
R
Martínez-Máñez
Félix
F
Sancenón
M Dolores
MD
Marcos
Pedro
P
Amorós
Carmen
C
Guillem
Enrique
E
Pérez-Payá
Ana
A
Costero
Salvador
S
Gil
Margarita
M
Parra
D000581:Amidohydrolases / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D002166:Camptothecin / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D005942:Gluconates / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D008247:Lysosomes / Q000378:metabolism; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
D000970:Antineoplastic Agents; D005942:Gluconates; C509968:MCM-41; C018954:gluconamide; D012822:Silicon Dioxide; D000581:Amidohydrolases; C019665:amidase; D002166:Camptothecin