Mesoporous Silica Nanoparticles Capped with Disulfide-Linked PEG Gatekeepers for Glutathione-Mediated Controlled Release

Abstract

Hybrid mesoporous silica nanoparticles (MSNs), which were synthesized using the co-condensation method and engineered with unique redox-responsive gatekeepers, were developed for studying the glutathione-mediated controlled release. These hybrid nanoparticles constitute a mesoporous silica core that can accommodate the guests (i.e., drug, dye) and the PEG shell that can be connected with the core via disulfide-linker. Interestingly, the PEG shell can be selectively detached from the inner core at tumor-relevant glutathione (GSH) levels and facilitate the release of the encapsulated guests at a controlled manner. The structure of the resulting hybrid nanoparticles (MSNs-SS-mPEG) was comprehensively characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and nitrogen adsorption/desorption isotherms analysis. The disulfide-linked PEG chains anchored on MSNs could serve as efficient gatekeepers to control the on-off of the pores. Compared with no GSH, fluorescein dye as the model drug loaded into MSNs showed rapid release in 10 mM GSH, indicating the accelerated release after the opening of the pores regulated by GSH. Confocal microscopy images showed a clear evidence of the dye-loaded MSNs-SS-mPEG nanoparticles endocytosis into MCF-7 cells and releasing guest molecules from the pore inside cells. Moreover, in vitro cell viability test using MTT assay indicated that MSNs-SS-mPEG nanoparticles had no obvious cytotoxicity. These results indicate that MSNs-SS-mPEG nanoparticles can be used in the biomedical field.

Multidrug Resistance in Cancer Circumvented Using a Cytosolic Drug Reservoir

“…Enrichment of Dox at the tumor site was observed after 48 h incubation with the NP‐drug in both Hela and ADR‐Hela models alike (Figure S12, Supporting Information). PEG is known to reduce the probability of nanoparticles being engulfed by phagocytic cells and also slow down the drug release from the nanoparticle carrier by capping the pores of the nanoparticle carrier 29. Literature reports showed that only ≈10% drug release is obtained in the first 24 h when PEG capping is employed 29, 30.…”

“…PEG is known to reduce the probability of nanoparticles being engulfed by phagocytic cells and also slow down the drug release from the nanoparticle carrier by capping the pores of the nanoparticle carrier 29. Literature reports showed that only ≈10% drug release is obtained in the first 24 h when PEG capping is employed 29, 30. Consequently, the prolonged blood circulation of the nanoparticles (with little drug release) due to PEG coating would result in a peak accumulation of the nanoparticles at longer hours, which was found at ≈48 h in the present work, as suggested by the in vivo imaging observation of strong tumor site florescence signal and reduced fluorescence intensity elsewhere in the mice at this time point (Figure S13, Supporting Information).…”

Biothiol-triggered, self-disassembled silica nanobeads for intracellular drug delivery

“…Most of the contemporary silica-based, biothiol-mediated release systems are established with similar setups. Cap or gatekeeper molecules such as collagen [34], DNA [35,36], polymer molecules [37,38], gold nanoparticles [39], and cyclodextrin [40,41] have been employed to functionalize the surface of mesoporous silica nanoparticles using disulfide linkers for enabling the redox-responsive off/on drug release. However, few studies [42,43] have focused on exploiting the inherent properties of silica materials to achieve self-modulations in the intracellular milieu and to improve cytosolic bioavailability.…”

Redox-responsive mesoporous silica as carriers for controlled drug delivery: A comparative study based on silica and PEG gatekeepers

“…Generally, TEM gives the size of particles in a dried state while DLS results in the hydrodynamic size of particles. MSN-SS-COOH and MSN-SS-PEG showed a larger D h than that of MSNs due to the modification of carboxyl groups and PEG chains, induced by carboxyl group-solvent interactions and chain-solvent interactions (Cui et al, 2012).…”

“…Recently, a few redox-responsive CDDSs using MSNs as carriers have been reported. For example, Liu et al (2008) (Cui et al, 2012). More recently, Liang Chen and co-workers (Chen et al, 2014) also used PEG as a gatekeeper for GSH-mediated drug delivery system.…”