The clinical efficacy of methotrexate (MTX) is limited by its poor water solubility, its\nlow bioavailability, and the development of resistance in cancer cells. Herein, we developed novel\nfolate redox-responsive chitosan (FTC) nanoparticles for intracellular MTX delivery. l-Cysteine and\nfolic acid molecules were selected to be covalently linked to chitosan in order to confer it redox\nresponsiveness and active targeting of folate receptors (FRs). NPs based on these novel polymers\ncould possess tumor specificity and a controlled drug release due to the overexpression of FRs and\nhigh concentration of reductive agents in the microenvironment of cancer cells. Nanoparticles (NPs)\nwere prepared using an ionotropic gelation technique and characterized in terms of size, morphology,\nand loading capacity. In vitro drug release profiles exhibited a glutathione (GSH) dependence.\nIn the normal physiological environment, NPs maintained good stability, whereas, in a reducing\nenvironment similar to tumor cells, the encapsulated MTX was promptly released. The anticancer\nactivity of MTX-loaded FTC-NPs was also studied by incubating HeLa cells with formulations for\nvarious time and concentration intervals. A significant reduction in viability was observed in a\ndose- and time-dependent manner. In particular, FTC-NPs showed a better inhibition effect on HeLa\ncancer cell proliferation compared to non-target chitosan-based NPs used as control. The selective\ncellular uptake of FTC-NPs via FRs was evaluated and confirmed by fluorescence microscopy. Overall,\nthe designed NPs provide an attractive strategy and potential platform for efficient intracellular\nanticancer drug delivery.
Loading....