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American Chemical Society, Langmuir, 41(28), p. 14766-14776, 2012

DOI: 10.1021/la303161e

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Design of enzyme-mediated controlled release systems based on silica mesoporous supports capped with ester-glycol groups

Journal article published in 2012 by Alessandro Agostini, Laura Mondragón Martínez ORCID, Elena Aznar Gimeno, Mª Carmen Coll Merino, Félix Sancenón Galarza, Ramón Martínez Mañez, Juan Soto Camino, María Dolores Marcos Martínez, Pedro Amoros Del Toro, Margarita Parra Alvarez, Pedro Amorós, Ana M. Costero, Salvador Gil Grau, Margarita Parra, Salvador Gil and other authors.
This paper was not found in any repository; the policy of its publisher is unknown or unclear.
This paper was not found in any repository; the policy of its publisher is unknown or unclear.

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Abstract

[EN] An ethylene glycol-capped hybrid material for the controlled release of molecules in the presence of esterase enzyme has been prepared. The final organic-inorganic hybrid solid S1 was synthesized by a two-step procedure. In the first step, the pores of an inorganic MCM-41 support (in the form of nanoparticles) were loaded with [Ru(bipy) 3]Cl 2 complex, and then, in the second step, the pore outlets were functionalized with ester glycol moieties that acted as molecular caps. In the absence of an enzyme, release of the complex from aqueous suspensions of S1 at pH 8.0 is inhibited due to the steric hindrance imposed by the bulky ester glycol moieties. Upon addition of esterase enzyme, delivery of the ruthenium complex was observed due to enzymatic hydrolysis of the ester bond in the anchored ester glycol derivative, inducing the release of oligo(ethylene glycol) fragments. Hydrolysis of the ester bond results in size reduction of the appended group, therefore allowing delivery of the entrapped cargo. The S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays with HeLa and MCF-7 cell lines, and were found to be associated with lysosomes, as shown by confocal microscopy. However, when S1 nanoparticles were filled with the cytotoxic drug camptothecin (S1-CPT), S1-CPT-treated cells undergo cell death as a result of S1-CPT cell internalization and subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate that induced the release of the camptothecin cargo. These findings point to a possible therapeutic application of these nanoparticles. © 2012 American Chemical Society. ; Spanish Government (Projects MAT2009 ; Generalitat Valencia (Project PROMETEO/2009 ; Agostini, A.; Mondragón Martínez, L.; Aznar Gimeno, E.; Coll Merino, MC.; Martínez Mañez, R.; Sancenón Galarza, F.; Soto Camino, J. (2012). Design of enzyme-mediated controlled release systems based on silica mesoporous supports capped with ester-glycol groups. LANGMUIR. 28:14766-14776. doi:10.1021/la303161e. ; Senia ; 14766 ; 14776 ; 28