Biocompatible Graphene Oxide Nanoparticle-Based Drug Delivery Platform for Tumor Microenvironment-Responsive Triggered Release of Doxorubicin

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Abstract

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.

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