A facile strategy was established to develop a drug delivery system (DDS) based on the graphene oxide nanoparticles (GON) with suitable size and shape to deliver drug effectively, by grafting the biocompatible PEGylated alginate (ALG-PEG) brushes onto the GON via the disulfide bridge bond. TEM analysis and drug-loading performance revealed that the 3-D nanoscaled, biocompatible, reduction-responsive nanocarriers (GON-Cy-ALG-PEG) were spherical in shape with diameters of 94.73 ± 9.56 nm. They possessed high doxorubicin (DOX)-loading capacity and excellent encapsulation efficiency, owing to their unique 3-D nanoscaled structure. They also had excellent stability in simulated physiological conditions and remarkable biocompatibility. Importantly, the in vitro release showed that the platform could not only prevent the leakage of the loaded DOX under physiological conditions but also detach the cytamine (Cy) modified PEGylated alginate (Cy-ALG-PEG) moieties, response to glutathione (GSH). Confocal microscopy and WST-1 assays provided clear evidence of the DOX-loaded GON-Cy-ALG-PEG endocytosis, whereas the drug-loaded nanocarriers exhibited high cytotoxicity to model cells. Furthermore, the cell apoptosis also was monitored via Flow cytometry. The results indicated that the DOX-loaded nanocarriers presented favorable efficiency of cell apoptosis. So these findings demonstrate that the accelerated release of the loaded DOX was realized in the presence of an elevated GSH that simulate the acidic endosomal compartments.

A novel graphene oxide nanoparticle (GON)-based drug delivery system containing GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride-modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated via the classic self-assembly of the deprotonated carboxyl of GONs and the protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA serves as the outmost layer. In this GON-based drug delivery system, the GON cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the π-π stacking interaction between the large π conjugated structures of GO and the aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells served as a smart protection screen to evade the premature release of the as-loaded DOX in normal extracellular condition, and then, the release of DOX was accelerated because of the detachment of chitosan coating at low pH. Furthermore, the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug delivery system with positive surface charge by taking advantage of the pH difference between physiological conditions and the tumor microenvironment to enhance the cellular uptake. Then, the pH-dependent site-specific drug release was realized. The in vitro investigations confirmed that these promising GON/CS/CS-DMMA hybrids with the charge-reversible character possessed various merits including excellent encapsulation efficiency, high stability under physiological conditions, enhanced cellular uptake by HepG2 cells, and tunable intracellular chemotherapeutic agent release profiles, proving its capability as an intelligent anticancer agent nanocarrier with enhanced therapeutic effects. This smart GON/CS/CS-DMMA vehicle with the surface charge-reversible character may be used as a significant drug delivery system for cancer treatment.

A facile and effective approach was established for fabricating core-shell-corona micelles by self-assembly of poly(ethylene glycol)-b-poly(acrylic acid-co-tert-butyl acrylate)-poly(ε-caprolactone) (PEG43-b-P(AA30-co-tBA18)-b-PCL53) triblock copolymer, synthesized via a combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), click chemistry, and hydrolyzation. The prenanovehicles with three different hydrolysis degrees from PEG43-b-PtBA48-b-PCL53 were developed to evaluate the drug loading capacity (DLC) and drug encapsulation efficiency (DEE). After cross-linking with a disulfide bond to regulate the drug release kinetics, the spherical core-shell-corona micelles with average diameter of 52 ± 4 nm were obtained in aqueous solution. The reduction-responsive cross-linked micelles showed a slow sustained release in normal physiological conditions and a rapid release upon exposure to simulated tumor intracellular conditions. In addition, the cytotoxic analysis and HepG2 cell growth inhibition assays demonstrated their remarkable biocompatibility and similar excellent anticancer activity as the free doxorubicin (DOX), which has also been revealed by the confocal laser scanning microscope (CLSM) analysis. So the reduction-sensitive core-shell-corona micelles are expected to be promising tumor microenvironment-responsive nanovehicles for hydrophobic drugs by glutathione (GSH) triggering.

The unique reduction-triggered functional graphene oxide nanoparticles (GON) with well-defined size and uniform distribution were designed as an innovative drug delivery platform for cancer treatment for the first time, via the redox radical polymerization of methacrylic acid from the polyethylene glycol (PEG) modified GON (GON-PEG), following by cross-linking with cystamine. Thermogravimetric analysis demonstrates that the typical PMAA2-GON-PEG carriers contain about 16 wt % PEG segments and 33 wt % poly(methacrylic acid) (PMAA) brushes. PEG moieties are incorporated to make the drug delivery platforms stealthy during blood circulation. Notably, introducing the cross-linked PMAA brushes efficiently minimizes the premature release of doxorubicin (DOX) in the stimulated normal tissues, and accelerates DOX release in the stimulated tumor tissues through response to reduce agent. The carriers showed a 6-fold faster releasing rate at pH 5.0 in the presence of 10 mM glutathione (GSH) (stimulated tumor tissues) than at pH 7.4 with 10 μM GSH (stimulated normal tissues). In vitro cytotoxicity test also showed that the cross-linked PMAA2-GON-PEG (CPMAA2-GON-PEG) carriers had remarkable cytocompatibility, and that the DOX-loaded CPMAA2-GON-PEG had excellent killing capability to SiHa cells.

A novel graphene oxide (GO)-based nanocarrier has been designed for the targeting and pH-responsive controlled release of anti-cancer drugs.