Multidisciplinary research at the forefront of the field of hybrid materials has paved the way to the development of endless examples of smart devices. One appealing concept in this fertile field is related to the design of gated materials. These are constructed for finely tuning the delivery of chemical or biochemical species from voids of porous supports to a solution in response to predefined stimuli. Such gated materials are composed mainly of two subunits: (i) a porous inorganic support in which a cargo is loaded and (ii) certain molecular or supramolecular entities, generally grafted onto the external surface, which can control mass transport from pores. On the basis of this concept, a large number of imaginative examples have been developed. This review intends to be a comprehensive analysis of papers published until 2014 on hybrid mesoporous gated materials. The molecules used as gates, the opening mechanisms, and controlled release behavior are detailed. We hope this review will not only help researchers who work in this field but also may open the minds of related ones to develop new advances in this fertile research area.

This paper proposes a new nanoscopic molecular movable gate-like functional hybrid system consisting of nanoscopic MCM-41-based material functionalized onto pore outlets with a saccharide derivative capable of interacting with boronic acid functionalized gold nanoparticles (AuNPs) acting as nanoscopic caps. The gating mechanism involves the reversible reaction between polyalcohols and boronic acids to form boronate esters. Functionalized AuNPs thus act as a suitable nanoscopic cap via the reversible formation of the corresponding boroester bonds with the saccharide derivative anchored on the external surface of the mesoporous silica-based solid. The developed platform operates in aqueous solution and can be triggered by two simple external stimuli such as pH changes or light. The hydrolysis of the boroester bond takes place at pH 3, which results in rapid delivery of the safranine cargo from the pore voids into the aqueous solution. However, at pH 5 the pores are capped with nanoparticles and the delivery is strongly inhibited. The kinetics of the delivery was studied at pH = 3, assuming a simple diffusion process and that the kinetics of guest release from the pore voids of the hybrid material can be explained by the Higuchi model. It is possible to deliver the cargo in small portions by carrying out on-off aperture cycles via changing the pH from 3 to 5. AuNPs also open the possibility of employing light as a suitable stimulus for release procedures using the AuNPs' capacity for raising their temperature locally by absorption of laser light. The plasmonic heating using a Nd:YAG laser at 1064 nm results in the cleavage of the boronic ester linkage that anchors the nanoparticles to the surface of the mesoporous silica-based material, allowing the release of the entrapped guests. Further studies also demonstrated that it is possible to fine-tune the amount of cargo delivered by simply controlling the laser irradiation opening the possibility to designing laser-induced pulsatile release supports.

Mondragón Martínez, L.; Aznar, E.; Marcos Martínez, MD.; Martínez-Máñez, R.; Sancenón Galarza, F.; Soto Camino, J.... (2010). Enzyme-responsive intracellular controlled release using nanometric silica mesoporous supports capped with "saccharides". ACS Nano. 4(11):6353-6368.

The great escape: A biocontrolled gated material has been prepared by grafting a lactose derivative onto the pore outlets of a mesoporous support. The galactosidase‐induced hydrolysis of the β1→4 glycosidic bond in the lactose moiety (red box in picture) allows the release of a dye entrapped in the pores of the hybrid material to the bulk solution.

Silica mesoporous supports (SMSs) have a large specific surface area and volume and are particularly exciting vehicles for delivery applications. Such container-like structures can be loaded with numerous different chemical substances, such as drugs and reporters. Gated systems also contain addressable functions at openings of voids, and cargo delivery can be controlled on-command using chemical, biochemical or physical stimuli. Many of these gated SMSs have been applied for drug delivery. However, fewer examples of their use in sensing protocols have been reported. The approach of applying SMSs in sensing uses another concept—that of loading pores with a reporter and designing a capping mechanism that is selectively opened in the presence of a target analyte, which results in the delivery of the reporter. According to this concept, we provide herein a complete compilation of published examples of probes based on the use of capped SMSs for sensing. Examples for the detection of anions, cations, small molecules and biomolecules are provided. The diverse range of gated silica mesoporous materials presented here highlights their usefulness in recognition protocols.

A two‐channel switchable nanoscopic hybrid system, able to modulate mass transport by photoresponsive appended organic groups and the presence of G1.5 PAMAM dendrimers as molecular caps, is reported. This new functional gatelike ensemble is chemically (by pH changes) and photochemically (using visible light) controlled in pure aqueous solution, as demonstrated by an experiment involving the controlled release of a dye (see figure).

A new gated nanodevice design able to control cargo delivery using glucose as trigger and cyclodextrin-modified glucose oxidase as capping agent is reported.Mass transport control at the nanometric level is a captivating area of research that has attracted the attention of scientists in the latest years. Especially, the development of gated systems able to retain a cargo and release it after the application of a stimulus has demonstrated to be an excellent approach for the development of smart nanodevices for advanced delivery applications. 1 In this context, silica mesoporous supports are widely used as inorganic scaffolds thanks to their unique characteristics such as high homogeneous porosity, inertness, robustness, thermal stability, the presence of tunable pore sizes, homogeneous pore distribution and high loading capacity. 2 Moreover, via decoration of the mesoporous material with a wide collection of organic moieties, linkers and capping agents, researchers have prepared nanovalves that can be triggered with target chemical 3 (such as redox molecules, selected anions, pH changes and biomolecules) physical 4 (such as light, temperature or magnetic fields) and biochemical (such as enzymes, antibodies, or DNA) stimuli. 5 In particular the development of enzyme-responsive bio-gated mesoporous silica nanoparticles is appealing. In previously reported examples tailor-made sequences anchored on the mesoporous support are hydrolized by target enzymes allowing the selective release of the entrapped cargo. However in these cases enzymes act as triggers but as far as we know there are not examples where enzymes were used as functional gating elements. 6 In this context, and as a new approach, we envisioned the potential design of gated materials in which the enzymes could act as caps and the uncapping process would be triggered by the product obtained by the enzyme's activity on a target substrate. The combination of the promising features of silica mesoporous supports as containers, enzymes as caps and substrates as trigger would result in a sophisticated but simple way to prepare selective substrate-responsive gated mesoporous materials for different applications. As a proof-of-concept we have selected herein glucose oxidase as capping enzyme and glucose as the substrate to trigger cargo release.The designed capped support is depicted in Scheme 1. It is based on the use of mesoporous silica nanoparticles loaded with a suitable reporter (i.e. ruthenium bipyridine complex) and containing anchored methylbenzymidazole moieties on the pore outlets. The mesopores are then capped with an active CDmodified-glucose oxidase (CD-GOx) through the formation of an inclusion complex between the cyclodextrins and the propylbenzymidazole group anchored to the solid support. The presence of the substrate glucose combined with the catalytic action of CD-GOx to produce gluconic acid was expected to induce protonation of the benzymidazole group that might result in the inclusion complex dethreating and the subsequent cargo release. Sc...

We report herein the design of a smart delivery system in which cargo delivery from capped mesoporous silica (MS) nanoparticles is controlled by an integrated enzyme-based "control unit". The system consists of Janus-type nanoparticles having opposing Au and MS faces, functionalized with a pH-responsive β-cyclodextrin-based supramolecular nanovalve on the MS surface and two effectors, glucose oxidase and esterase, immobilized on the Au face. The nanodevice behaves as an enzymatic logical OR operator which is selectively fueled by the presence of D-glucose and ethyl butyrate.