Study the anticancer efficacy of doxorubicin-loaded redox-responsive chitosan-derived nanoparticles in the MDA-MB-231 cell line

• Published in: Carbohydrate research Vol. 536; p. 109049
• Main Authors: Antoniraj, Mariya Gover, Dhayanandamoorthy, Yamini, Ponnuchamy, Kumar, Kandasamy, Ruckmani, Pandima Devi, Kasi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2024
• Subjects: Breast cancer; Dithiodipropionic acid; Doxorubicin; Glutathione; Methoxy poly(ethylene glycol); Redox responsive nanoparticles; Redox responsive nanoparticles; Breast cancer; Methoxy poly(ethylene glycol); Dithiodipropionic acid; Doxorubicin; Glutathione
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2024.109049

This study focuses on the design and evaluation of redox-responsive nanoparticles (NPs) by synthesizing disulfide-containing N-phthaloyl chitosan–SS–methoxy poly(ethylene glycol) (NPC-SS-mPEG) and incorporating the anti-cancer drug doxorubicin into the NPs. The structural features of NPC-SS-mPEG were investigated using FTIR, NMR, XRD, and TGA/DTA analysis. DLS and TEM analysis confirmed the particle size and morphology of the NPs. The stability of the NPs was measured with the presence and absence of glutathione (GSH) in buffers pH 5 and 7.4. Furthermore, the release of DOX from the NPs was studied in GSH (10 mM) containing/absent medium at pH 5 and pH 7.4 which mimics the intracellular environment with redox potential. The results indicated a significantly increased release of DOX in the GSH containing medium pH 5 (82.9 ± 2.1 %) and pH 7.4 (67.37 ± 0.88 %) compared to the GSH free pH 7.4 (29.99 ± 1.01 %) and pH 5 medium (56.56 ± 1.7 %) at 60 h. The cytotoxicity study in the MDA-MB-231 breast cancer cell line by MTT assay indicated higher toxicity of redox-responsive NPs to cancer cells than free DOX. In concurrence with the cytotoxicity assay, in-vitro fluorescence staining assays (AO/EB, Hoechst, ROS generation) also confirmed that NPs loaded with DOX induce higher toxicity to cancer cells than free DOX. Taken together, the overall results confirmed the superiority of the redox response-mediated release of DOX in effectively controlling cancer progression. [Display omitted] •Disulfide linked redox responsive Chitosan–SS–mPEG carrier was synthesized.•A redox-responsive nanocarrier loaded with doxorubicin was formulated.•Nanoparticles could destabilize and release drugs through a redox response mechanism.•The cell culture studies have confirmed the anti-cancer activity of the redox-responsive nanoparticles.