pH and Glutathione Dual-Responsive Dynamic Cross-Linked Supramolecular Network on Mesoporous Silica Nanoparticles for Controlled Anticancer Drug Release

Abstract

A dynamic cross-linked supramolecular network of poly(glycidyl methacrylate)s derivative chains was constructed on mesoporous silica nanoparticles via disulfide bond and ion-dipole interactions between cucurbit[7]urils and protonated diamines in the polymer chains. This kind of multifunctional organic-inorganic hybrid material with pH- and glutathione- (GSH-) stimuli responsiveness can be applied to anticancer drug delivery and controlled release. Good release performance toward doxorubicin hydrochloride (DOX) was achieved under the simulative tumor intracellular environment (pH = 5.0, CGSH = 2-10 mM). Significantly, the release amount of DOX increased upon lowering the solution pH value and increasing the concentration of GSH, as demonstrated by a series of controlled release experiments. Furthermore, the DOX-loaded hybrid nanomaterials displayed apparent cell-growth inhibition effects to cancer cell lines, as evidenced by MTT assay and confocal laser scanning microscopy.

Polymer Brush Decorated MOF Nanoparticles Loaded with AIEgen, Anticancer Drug, and Supramolecular Glue for Regulating and In Situ Observing DOX Release

“…Besides, to minimize the potential cell membrane destabilization caused by the crowded positive charges of polymer brushes on MOFs, we chose to employ cucurbit[7]uril (CB[7]) for specific binding to amino groups of the polymer brushes . Note that the binding of CB[7] to the positively charged amino groups follows a distinctive pH‐dependent manner, where the supramolecular interactions decrease dramatically at lower pH of tumor microenvironment due to the weakening of host–guest binding interactions . Hence, the electrostatically formulated UiO‐PGEDA/TPE&DOX/CB[7] complex could be subjected to structural rearrangement, potentially facilitating the release of DOX from the polymer brush decorated MOF architecture once entrapped in a subcellular pH gradient, eventually conducing to favorable drug transportation and drug release behaviors for ultimate anticancer outcome (Scheme ).…”

Silica‐based organic‐inorganic hybrid nanoparticles and nanoconjugates for improved anticancer drug delivery

“…The pH sensing functions are of prime importance in MSN-based triggered-release nanocarriers. In another study, DOX hydrochloride was released by responding to acidic tumour intracellular environment [55]. Indeed, many of hybrid materials prepared for controlled drug release on tumor location were often based on pH or glutathione (GSH) level changes because of acidic pH (5.0) and high GSH concentration levels (2−10 mM) on tumour intracellular environment compared with normal tissues [54].…”

Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection

“…The solution is then filtered, frozen, and lyophilized with mannitol (Kuo, 2005). A 2015 study utilized a hybrid nanoparticle consisting of a network of poly(glycidyl methacrylate) chains secured to a silica nanoparticle (Li et al 2015). Li et al found this type of hybrid nanoparticle to be an ideal anti-cancer drug carrier, specifically of DOX (Li et al 2015).…”

“…A 2015 study utilized a hybrid nanoparticle consisting of a network of poly(glycidyl methacrylate) chains secured to a silica nanoparticle (Li et al 2015). Li et al found this type of hybrid nanoparticle to be an ideal anti-cancer drug carrier, specifically of DOX (Li et al 2015). The DOX-loaded nanoparticles were effective in inhibiting the growth of the cancer cell line, A549 (Li et al 2015).…”

“…Li et al found this type of hybrid nanoparticle to be an ideal anti-cancer drug carrier, specifically of DOX (Li et al 2015). The DOX-loaded nanoparticles were effective in inhibiting the growth of the cancer cell line, A549 (Li et al 2015). …”