The Study Of Functionalized Graphene Oxide-based In Situ Hydrogel Loaded With Docetaxel

With the continual emergence of new anticancer drugs, chemotherapy shows unique advantages and broad prospects. However, these drugs have no selectivity to tumor cells. In situ hydrogel as an intelligent temperature-sensitive drug delivery system has low toxicity and good biocompatibility, and has shown better potentials in drug release area. Graphene Oxide (GO) has single atomic layer structure and large surface area, and could load aromatic drugs through non-covalent bonds. So GO may be potential drug carrier material. Besides, GO has strong absorption in the near infrared laser area and could be used for hyperthermia therapy of tumor.A functionalized graphene oxide-based in situ hydrogel loaded with docetaxel was constructed in this project to enhance antitumor efficacy and reduce side effects of DTX. Firstly, GO was functionalized with chitosan (CS) to increase the stability and biocompatibility of GO in physiological solutions. Then insoluble drug Docetaxel (DTX) was loaded onto GO-CS to get GO-CS/DTX via non-covalent bonds, and then GO-CS/DTX were lyophilized into powders. We adopted cold dissolution method to prepare blank hydrogel solutions, which were mixed with GO-CS/DTX powders to obtain the final formulation GO-CS/DTX-gel.The Michigan Cancer Foundation-7 (MCF-7) cells were chosed as tumor cells mode to study the anti-tumor effects of GO-CS/DTX combining with the near infrared laser. The results showed that 90% of MCF-7 cells could take in GO-CS/DTX within 4h, which improved the efficiency of membrane permeability of DTX. GO-CS/DTX showed higher growth inhibitory effect on MCF-7 cells than that of DTX, and there was significant improved curative effect. Cell cycle and cell apoptosis results showed that GO-CS/DTX combining with 808nm laser could produce synergistic effect of hyperthermia therapy with chemo-therapy, and induced more MCF-7 cells apoptosis.S180 beaing mice were chosed as the model animals. The tumor volume and body weight of mice were measured periodically during the experiment. The H&E and TUNEL staining of heart, liver and tumor tissues were used to observe the psychology changes. The results showed that the anti-tumor effect of GO-CS/ DTX-gel was the best, and the tumor apoptosis rates were more remarkable when combined with 808nm laser radiation. In addition, the imaging instrument in vivo was used to study the real-time tracking of GO-CS/DTX-gel in the body of S180 bearing mice. The results confirmed that GO-CS/DTX-gel could extend the residence time of DTX in tumor tissues, and showed no obvious toxicity to major organs of the mice in the experimental dosage range.