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

Abstract

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]Cl2 complex and then, in the second step, the outer of the pores were functionalized with ester-glycol moieties than acted as molecular caps. In the absence of an enzyme the 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 the addition of esterase enzyme, delivery of the ruthenium complex was observed due to the enzymatic hydrolysis of the ester bond in the anchored ester-glycol derivative inducing the release of oligo(ethylene glycol) fragments. The hydrolysis of the ester bond results in a size reduction of the appended group therefore allowing the delivery of the entrapped cargo. The S1 nanoparticles were not toxic for cells as demonstrated by cell viability assays using HeLa and MCF-7 cell lines and found associated to lysosomes as shown by confocal microscopy. However when S1 nanoparticles were filled with the 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 therapeutical application of these nanoparticles.