Glutathione functionalized mesoporous organosilica conjugate for drug delivery

Abstract

A novel pH-responsive drug delivery system, based on permeation-enhancing glutathione (GSH) and pH sensitive polyacrylic acid (PAA) grafted mesoporous organosilica nanocarriers (MONs), is developed. PAA grafted MONs are prepared via a facile grafting-to strategy and then GSH is conjugated on the PAA chain via an amidation reaction. The resultant MONs-PAA-GSH conjugate not only shows an efficient drug loading efficiency but also offers a superb binding capability to cell membranes. With doxorubicin hydrochloride (DOX) as a model, a loading efficiency of 43.7% is readily achieved for 1.0 mg mL À1 DOX in 1.0 mL aqueous medium with 1.0 mg of MONs-PAA-GSH conjugate. The ensuing release of DOX from the DOX-MONs-PAA-GSH conjugate is pH-dependent, offering release efficiencies of 70.2% (pH 3.0), 45.5% (pH 5.0) and 16.1% (pH 6.5), within 24 h. The MONs-PAA-GSH conjugate displays favorable cellular uptake properties, minimum cytotoxic effect or excellent biocompatibility in comparison with those for MONs-PAA. It is demonstrated that the MONs-PAA-GSH conjugate serves as a promising platform for building a controlled drug delivery system.

Mesoporous organosilica nanoparticles: Degradation strategies and application in tumor therapy

“…On the other hand, by incubating with Hela cells, the MONs-PAA and MONs-PAA-GSH are biocompatible, but the DOX-MONs-PAA-GSH group showed the lowest cell viability (<40% cell viability at a concentration of 10 ppm), indicating that the MONs-PAA-GSH as drug nanocarriers would be promising for tumor chemotherapy. 82 Zhang et al proposed to integrate the thioether-bridged MONs with Cy5.5 and pH (low) insertion peptide (pHLIP) to construct a TME-responsive drug delivery system (MONs-Cy5.5-pHLIP) (Figure 4A). 83 The results showed that the antitumor drug DOX could be efficiently loaded by MONs with 334 mg/g, and the DOX release from the DOX@MONs-Cy5.5-pHLIP in the 5 μM and 10 μM GSH solutions were estimated to be 52.34% and 63.67%, respectively.…”

Overview of stimuli-responsive mesoporous organosilica nanocarriers for drug delivery

“…In this way, the packing of these coated pore template structures results in the formation of the nanoparticles [9]. If a mixture of tetraalkyl silicates and organosilanes is used the particles are usually denominated as MONs, whereas the solo utilization of organosilanes originates the PMOs [47][48][49]. After the organosilica nanoparticles' synthesis, the soft pore template must be removed to allow the subsequent loading of the therapeutic agents and due to biocompatibility issues (e.g.…”

“…After the organosilica nanoparticles' synthesis, the soft pore template must be removed to allow the subsequent loading of the therapeutic agents and due to biocompatibility issues (e.g. the CTAB is highly cytotoxic) [47,49]. In contrast to the MSNs, the purification of organosilica nanoparticles demands the utilization of less aggressive extraction procedures in order to preserve the organic content [30].…”

“…Particularly, in tumor drug delivery applications, the presence of the organic bridges on the silica matrix impacts on their chemical properties, which can be explored to tune the hydrophobicity/ hydrophilicity or even the surface charge of the pore walls in order to maximize the drug loading [20,65,66]. In this way, the drug encapsulation in the organosilica nanoparticles pores can be achieved through nanoparticles/drug dispersion methods in order to stimulate electrostatic or hydrophobic/hydrophilic interactions between the therapeutic molecules and the nanoparticle pores [47,67].…”

“…This approach aims to take advantage of the natural pH gradient that the nanoparticles will encounter when circulating in the human body [21]. During the nanoparticles' circulation in the bloodstream, they will be exposed to a neutral pH value (∼7.4), however when reaching the tumor tissue the pH decreases to acidic values (around to 6.5) [47,73,74]. Such difference is attributed to the limited availability of oxygen and nutrients that favor the lactate production (i.e.…”