Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles

Abstract

Royal Society of ChemistryCandel Busquets, I.; Aznar Gimeno, E.; Mondragón Martínez, L.; Martínez Mañez, R.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2012). Amidaseresponsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles. Nanoscale. 4 (22) TMCM-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 enzyme, a zero release system was obtained. S1 was prepared by loading nanoparticles 10 with safranine O dye and was then capped with a gluconamide derivative. In the absence of enzyme, 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 15 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-CPTunderwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated 20 hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo.

New Oleic Acid‐Capped Mesoporous Silica Particles as Surfactant‐Responsive Delivery Systems

“…The opportunity of functionalizing the external surface of the MSPs with capping agents and uncap them with predefined stimuli makes these supports ideal candidates for controlled delivery applications. A number of examples able to payload deliver in the presence of physical, chemical and biochemical stimuli have been widely described …”

“…A number of examples able to payload deliver in the presence of physical, chemical and biochemical stimuli have been widely described. [14][15][16][17][18] Despite these reported examples, the design of MSPs gated materials able to control the delivery through the action of surfactants is still emerging. To the best of our knowledge, only one example involving surfactant-responsive mesoporous silica particles has been recently described.…”

Mesoporous Silica‐Based Materials with Bactericidal Properties

“…Moreover, the pore‐blockers should respond to appropriate external or internal triggers to close or open the well‐defined pores, causing on‐demand intelligent cargo delivery . Various porekeepers including polymers (e.g., polymer poly(2‐vinylpyridine) (PVP), poly(N‐succinimidyl acrylate), poly(2‐dimethylaminoethyl methacrylate), poly(acrylic acid) brush), host–guest assemblies (e.g., Cyclodextrins, cucurbit,uril, pillararenes), inorganic nanomaterials (e.g., Au NPs, quantum dots, Ag NPs, cerium oxide NPs, manganese oxide NPs, and reduced graphene), and biomacromolecules (e.g., peptides, nucleic acids, saccharides, and proteins) have been employed under certain internal or external stimuli, such as pH, temperature, light, redox potential, ultrasound, small molecules, biomolecules, and or a combination of these stimuli, to achieve controllable DDSs based on mesoporous silica nanoparticles (MSNs) …”

Polymer‐Brush‐Grafted Mesoporous Silica Nanoparticles for Triggered Drug Delivery

“…In addition, other MSNs‐based nanoplatforms employing gluconamide and ϵ‐poly‐L‐lysine as gated materials for enzyme‐driven gate‐opening drug release for cancer therapy have been reported. For example, Candel et al . synthesized enzyme responsive MSNs using amidase as biological‐keys to uncap the gatekeeper polymer gluconamide through hydrolysis of amide bonds.…”