Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. Regarding their specific conditions, such as acidic pH, drug carriers to treatment of tumor microenvironment need some criteria to enhance drug delivery efficiency. In this study, for the first time, pH-sensitive BSA-stabilized graphene (BSG)/chitosan nanocomposites were synthesized through electrostatic interactions between the positively charged chitosan nanoparticles and negatively charged BSG and used for Doxorubicin (DOX) encapsulation as a general anticancer drug. Physicochemical characterization of the nanocomposites with different concentrations of BSG (0.5, 2, and 5wt%) showed effective decoration of chitosan nanoparticles on BSG. Comparing DOX release behavior from the nanocomposites and free BSG-chitosan nanoparticles were evaluated at two pHs of 7.4 and 4.5 in 28 days. It was shown that the presence of BSG significantly reduced the burst release observed in chitosan nanoparticles. The nanocomposite of 2wt% BSG was selected as the optimal nanocomposite with a release of 84% in 28 days and with the most uniform release in 24 h. Furthermore, the fitting of release data with four models including zero-order, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. It was also demonstrated that DOX released from the nanocomposite had a significant effect on the suppression of cancer cell proliferation at acidic pH.
Drug delivery is one of the major issues in the world of science, which receives a large part of the research in various fields. The ultimate goal of drug delivery is to help the patient with developing advanced drug delivery systems. These systems revolutionize the treatment of many diseases including cancer. Effective drug carriers can significantly reduce the undesirable side effects of anticancer drugs through the drug controlled release and using the selective drug to cancerous tissue. The natural biocompatible and biodegradable polymer of chitosan is widely investigated in drug delivery systems, especially as the carrier for anticancer drugs. An important aspect for the application of chitosan in drug delivery for cancer treatment is its pH sensitivity. Graphene attracted much attention in various fields as a shining star in the science of materials. In recent years, the use of graphene in the diagnosis and treatment of cancer is also investigated. Therefore, chitosan-graphene nanocomposite can be introduced as a pH-sensitive carrier for cancer theragnosis. In the current study, the application of chitosan and graphene in the treatment of cancer addressed in previous years was discussed.
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