Hyaluronic Acid-Decorated Graphene Oxide Nanohybrids as Nanocarriers for Targeted and pH-Responsive Anticancer Drug Delivery

Abstract

A novel nanohybrid of hyaluronic acid (HA)-decorated graphene oxide (GO) was fabricated as a targeted and pH-responsive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for tumor therapy. For the preparation, DOX was first loaded onto GO nanocarriers via π-π stacking and hydrogen-bonding interactions, and then it was decorated with HA to produce HA-GO-DOX nanohybrids via H-bonding interactions. In this strategy, HA served as both a targeting moiety and a hydrophilic group, making the as-prepared nanohybrids targeting, stable, and disperse. A high loading efficiency (42.9%) of DOX on the nanohybrids was also obtained. Cumulative DOX release from HA-GO-DOX was faster in pH 5.3 phosphate-buffered saline solution than that in pH 7.4, providing the basis for pH-response DOX release in the slightly acidic environment of tumor cells, while the much-slower DOX release from HA-GO-DOX than DOX showed the sustained drug-release capability of the nanohybrids. Fluorescent images of cellular uptake and cell viability analysis studies illustrated that these HA-GO-DOX nanohybrids significantly enhanced DOX accumulation in HA-targeted HepG2 cancer cells compared to HA-nontargeted RBMEC cells and subsequently induced selective cytotoxicity to HepG2 cells. In vivo antitumor efficiency of HA-GO-DOX nanohybrids showed obviously enhanced tumor inhibition rate for H22 hepatic cancer cell-bearing mice compared with free DOX and the GO-DOX formulation. These studies suggest that the HA-GO-DOX nanohybrids have potential clinical applications for anticancer drug delivery.

pH and glutathione dual-triggered supramolecular assemblies as synergistic and controlled drug release carriers

“…50 All other reagents were of analytical grade and used directly without further purification and water was redistilled freshly. 1 H NMR spectra, 13 C NMR spectra and 2D nuclear overhauser enhancement spectroscopy (2D NOESY) 1 General Instrument Co. Ltd, China. Mass spectrometry analysis was studied on a Finnigan LCQDECA (ThermoQuest LC/ MS Division, San Jose, CA, USA) equipped with an electrospray ionization source (ESI) in positive and negative mode with a scan range of m/z 100-2000.…”

Polymer-drug conjugates as inhalable drug delivery systems: A review

“…HA can therefore be used either as a surface coating on nanoparticles, or as a direct drug carrier via conjugation. HA can also be used as a tumour-targeting moiety since it binds to CD44, a transmembrane glycoprotein which is commonly overexpressed on the surface of cancer cells [94,95]. However, in healthy cells CD44 is highly glycosylated which limits its capacity to bind to HA [96].…”

Recent Advances in the Synthesis of Graphene-Based Nanomaterials for Controlled Drug Delivery

“…Therefore, the pH differences inside the body can be used to improve targeted drug delivery [68]. For example, HA-, RC-, and LA-functionalized GO were demonstrated exhibiting a pH sensitive anticancer drug release behavior [50][51][52].…”

“…The loading amount of epirubicin on HA-GO increased significantly with an increasing of the pH of epirubicin solutions, which is beneficial for the release of drug in the acidic environment of tumor ( Figure 6). In other cases, HA-GO nanohybrids have been utilized for the pH-responsive delivery of DOX for tumor therapy [50,82].…”