Stimuli-responsive functionalized mesoporous silica nanoparticles for drug release in response to various biological stimuli

Abstract

A silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system has been synthesized and characterized. The system uses L-cysteine derivatized gold nanoparticles (AuNPs), bound to the MSNs using Cu 2+ as a bridging ion. The AuNPs serve as removable caps that hinder the release of drug molecules inside the amino functionalized MSN mesoporous framework. The modified MSNs themselves exhibit negligible cytotoxicity to living cells, as revealed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The drug delivery system requires one of two biological stimuli to trigger drug release. These stimuli are either: low pH (pH < 5); or elevated levels of adenosine triphosphate (ATP) (concentration > 4 mM). The feasibility of biologically controlled release was demonstrated through the stimuli-induced removal of the AuNP caps over the MSN releasing the anticancer drug doxorubicin. We envisage that this MSN system could play a significant role in developing new generations of controlled-release delivery vehicles.

pH-responsive release of chlorhexidine from modified nanoporous silica nanoparticles for dental applications

“…Various stimuli were investigated, such as pH value [46][47][48][49], irradiation [50,51], temperature [52,53], redox potential [54], enzymatic activity [8] as well as specific antibodies [55] or glucose [56]. Systems using the irreversible cleavage of a chemical bond to remove pore-blocking gate keepers [57][58][59] only lead to a singular release that continues even after the stimulus has disappeared. A stimulus-responsive system working reversible would be more favorable for the desired long-term applications.…”

Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications

“…Some of the last reports in surface functionalization of MSP obtained from a TEOS sol-gel process are summarized in Table 2. It may be seen that most of the particles are type MCM-41 [78,79,[94][95][96][97][98][99], and few of them are from MCM-48 [100] or HMM [84]. All the others are catalogued as MSN [101][102][103][104][105][106][107][108], showing proof of mesostructured matrices with 2-4 nm average pore size, with exceptional sizes of 8 and 13 nm for HMM.…”

“…Precise control over the release kinetics without initial burst upon placement of the nanocarrier in the medium and accurate regulation of the drug release to achieve a stable profile is still required [72,76,77]. Recently, modified MSN have shown zero premature release, which is a useful property for delivery of toxic loads, i.e., antitumor drugs, where exact dosages must be administered [78,79]. Modification of MSN surface may be achieved through chemical functionalization with molecular (i.e., organic compounds or inorganic nanocrystals) or supramolecular ensembles (i.e., polymer layers, dendrimers).…”

“…Snap-top cap molecules such as b-cyclodextrin (b-CD) are proposed to be photoresponsive [87], while i-motif quadruplex DNA [101] capped-MSN have been proposed for pH-switchable nanocontainers, as well as metal-latched nanogates [96] that can trap or release molecules upon pH variation from Lewis base chelating groups. Others pH-responsive mechanisms include rhodamine B/benzidine conjugates that act as nanopistons [94] in the cylindrical space of b-CD rings placed around the orifices of the pores, or L-cysteine functionalized gold nanoparticles [78] attached to the MSN surface by ligand bonds through Cu 2? ions, that react also upon variation of ATP concentrations.…”

Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

“…S1B, black line), in which 10, 11 and 20 diffraction peaks of p6mm mesostructure were observed. This type of MSNs is particularly chosen in current study because of its simplicity in synthesis and popularity in drug delivery applications [5,31,41,42]. NMSNs are positively charged and the sample exhibited a zeta potential of 38.97 ± 1.2 mV in phosphate buffer solution.…”