Glutathione-responsive FA-CMC-GNA nanoparticles: a novel approach for enhanced delivery of gambogenic acid in lung cancer treatment

One of the limitations of current anticancer nanomedicines in clinical applications is the efficiency of drug delivery in their nanocarrier systems. Therefore, we aimed to develop a nano-delivery system loaded with a hydrophobic drug for lung cancer treatment. Nanoparticles (FA-CMC-GNA NPs) were prepared using an emulsion solvent evaporation method, with a disulfide bond-crosslinked thiolated carboxymethyl cellulose as the backbone, encapsulating the hydrophobic drug gambogenic acid. The preparation process was optimized through single-factor experiments and response surface methodology to determine the optimal preparation conditions. The characterization of the physicochemical properties of FA-CMC-GNA NPs was conducted using various techniques, including scanning electron microscopy, dynamic light scattering, X-ray spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The results showed that the nanoparticles exhibited uniform dispersion and spherical morphology with a particle size of approximately 193.3 nm. Additionally, FA-CMC-GNA NPs demonstrated significant glutathione (GSH)-responsive release behavior in vitro. The prepared FA-CMC-GNA NPs were internalized into A549 cells via folate receptor-mediated endocytosis and released gambogenic acid in response to GSH, resulting in a significant inhibitory effect on A549 cells. In conclusion, these findings suggest that FA-CMC-GNA NPs hold the potential to enhance the clinical application value of the hydrophobic drug gambogenic acid for lung cancer therapy.