Study On PEG-PDI/?-CD Gel For Chemotherapy-Photothermal Combined Therapy And Enhance The Antitumor Effect Of Curcumin Nanoparticle

BackgroundCancer,as one of the major causes threatening human health,has attracted much attention.Traditional treatment methods include surgery,chemotherapy,radiotherapy and biological therapy.Research on cancer has continuously made some achievements.However,many problems in clinical treatment and related research need to be solved urgently.For example,chemotherapy often leads to systemic toxic and side effects due to the drug's poor targeting and controllability,which causes body damage to patients or experimental subjects.Supramolecular hydrogels have a good sustained-release effect.Traditional medicines treated with gel carriers can significantly reduce the number of medications,improve drug bioavailability,and reduce toxic and side effects.On the other hand,photothermal therapy has been a research hotspot in recent years.Compared with chemotherapy,it has obvious advantages in biosafety.In combination with traditional chemotherapy,it is expected to significantly improve the tumor killing effect and reduce the side effects of chemotherapy.At present,many promising traditional drugs are limited in their transformation due to their low bioavailability.Research progress in nanomedicine has partially solved some problems,but still faces many challenges.For example,curcumin is limited in its application due to its poor bioavailability.Although the development of carrier-free self-assembled curcumin nanoparticles has improved the possibility of curcumin bioavailability,it has not achieved a sufficiently satisfactory effect.Combined with the experience of gel advantages,if curcumin nanoparticles are encapsulated in a gel carrier,it is expected to obtain a good sustained-release effect,to achieve the purpose of reducing the number of medications and improving the anti-tumor effect.Perylene diimide(PDI)and its derivatives have good photothermal and chemical stability,easy modification,and excellent biocompatibility,and have been widely used in many fields.In the past research reports,there have been many medical achievements related to PDI,such as fluorescence imaging,photodynamic and photothermal treatment.However,few studies have reported on the combination of its excellent properties with the gel drug delivery system,so it is of great exploration and prospective significance to develop the gel system based on PDI and further study and applicationThis experiment based on PDI by Polyethylene glycol(PEG),and Alpha-Cyclodextrin(?-CD)was prepared by interaction between subject and object can carry medicine supramolecular gel.In this paper,PEG-PDI/?-CD gel was used as the carrier material in two aspects:on the one hand,Indocyanine green(ICG)and Adriamycin(DOX)were used as the carrier material for chemotherapy-photothermal combination therapy to solve the problems related to traditional single chemotherapy;on the other hand,combined The curative effect of preparing curcumin nanoparticles by themselves is not good.After trying to combine the advantages of gel carrier,can nano-medicine improve the tumor-killing effect.Experimental demonstrations at the cell and animal level show that PEG-PDI/?-CD gel has a good sustained-release effect,a significant combination of chemotherapy and photothermal treatment,and the ability to enhance the antitumor effect of curcumin nanoparticles.ObjectiveA gel-loaded drug system capable of encapsulating chemotherapy-photothermal drugs for combined therapy and enhancing the bioavailability of curcumin nanoparticles was prepared,and tumor killing effects were compared through cell and animal experiments.Method1.Optimization and characterization of PEG-PDI/?-CD gel preparation:UV spectrum,nuclear magnetic hydrogen spectrum.2.PEG-PDI/?-CD gel sustained-release effect:The cumulative release rates at different pH values were measured separately.3.Photothermal effect detection:different concentrations of solution,different power irradiation for 5 min,recording temperature and taking pictures.4.In vitro experiments:1)Cell proliferation experiment:The toxicity to various cells was detected by CCK-8 method.2)AO/EB double staining experiment:Toxicity to various cells was determined by AO/EB double staining experiment.3)Apoptosis experiment:Annexin V-FITC/PI experiment was used to determine apoptosis.5.In vivo experiments:1)Modeling and group processing:subcutaneous injection for tumor modeling.Tumors were randomly divided into groups of approximately 100 mm3 with 5 animals in each group.2)Evaluation of antitumor effect:The tumor volume and weight of each experimental group were recorded,and the antitumor effect was compared and evaluated.3)Histological evaluation:HE staining of organs and tumor tissues.Result1.A new type of PEG-PDI/?-CD gel was successfully prepared.The in vitro release experiment showed pH response.The dissolution experiment and the in vitro release test proved that the gel has a good sustained release effect2.Cell proliferation experiments confirmed that 48 hours of incubation after adding the drug could detect the exact therapeutic effect,and the results of the AO/EB double staining experiment and the in vivo experiment were consistent.It was confirmed that PEG-PDI/?-CD gel was more effective in the combination of chemotherapy and photothermal treatment.Compared with traditional chemotherapy,not only can reduce the number of medications,and the advantages of chemotherapy and photothermal therapy are complementary,and because of the advantages of PEG-PDI/?-CD gel carrier,the final antitumor effect is better.3.The results of in vitro experiments CCK-8 show that curcumin nanoparticles can enhance curcumin treatment effect,and the addition of PEG-PDI/?-CD gel further enhances antitumor effect.AO/EB double staining experiments,flow cytometry and in vivo experiments are consistent.All confirmed that PEG-PDI/?-CD gel can further improve the bioavailability of curcumin nanoparticles and enhance the antitumor effect4.The results of the biosafety evaluation showed that the PEG-PDI/?-CD gel-loaded drug system did not show significant cytotoxicity at the cell and tissue research level,indicating that PEG-PDI/?-CD has good biocompatibility high security.In conclusion1.A new gel-loading system with good sustained-release effect was successfully prepared2.Both in vitro and in vitro experiments have shown that PEG-PDI/?-CD gel co-loading DOX and ICG combined treatment has no obvious toxic and side effects on normal tissues,but has significant killing effect on tumor tissues.3.It was also confirmed that the antitumor effect was enhanced after the curcumin nanoparticles were encapsulated by PEG-PDI/?-CD gel.