Anticancer Research Of Metal Complexes And Thermosensitive Hydrogel

Metal complexes have good antitumor activity and function of biological imaging.But it has some disadvantage,such as toxic and side effects,crossed drug resistance,low cellular uptake efficacy and rapid clearance in vivo.Therefore,improving anti-tumor drugs by targeting strategy and nanotechnology have become the focus in the development of novel tumor diagnosis and treatment agent.In this paper,we studied platinum complex,targeted ruthenium complexes and thermosensitive hydrogel.We found that they all had good antitumor activity in vivo.The main research results were as follows:1.We established the nude mice model that loaded MDA-MB-231 xenografts to study the in vivo antitumor activity of one platinum complex(Pt).We studied the change of tumor volume,weight and immunohistochemical analysis.These results showed that the platinum complex had good antitumor activity.Immunohistochemical analysis results also showed that the platinum complex reduced the expression of CD34 and Ki67,and raised the expression of Cleaved-caspase-3 and TUNEL fluorescent signal in tumor tissue.2.It is considered that metal ruthenium complexes are promising antitumor drugs.So,we studied the application of tumor diagnosis and treatment of the ruthenium complexes.We studied the targeted closed experiment,co-culture experiments and animal fluorescence imaging experiments.These results indicated the Ru-RGD could selectively accumulate in tumor cells and stay for a long period in tumor tissues.Moreover,we established the nude mice model that loaded Caski xenografts to study the in vivo antitumor activity of Ru-RGD and Ru-1.The change of tumor volume and tumor weight showed that the antitumor activity of Ru-RGD was higher than Ru-1.We also studied the application of Ru-RGD as tumor diagnosis reagent by immunofluorescence labeling technology.The results showed that Ru-RGD was a significant marker for cervical cancer tissue biopsies which were from the patients of different clinical stages.3.Thermosensitive hydrogel have an advantage on drug sustained release.It has broad application prospect.So,we synthesized the PLGA-PEG-PLGA polymer as the drug carrier.Then we loaded sorafenib,Se nanoparticles and ultra-fluid lipiodol to PLGA-PEG-PLGA to obtain thermo-sensitive Gel-SOR-LUF-Se NPs.The in vitro degradation experiment and rheology analysis results showed that Gel-SOR-LUF-Se NPs was injectable and biodegradable.Moreover,the in vivo antitumor results showed that the Gel-SOR-LUF-Se NPs had good antitumor activity.The results of immunohistochemical analysis also showed that the Gel-SOR-LUF-Se NPs reduced the expression of CD34 and Ki67,and raised the expression of Cleaved-caspase-3 in tumor tissue.H&E staining and blood biochemical index results showed that the Gel-SOR-LUF-Se NPs+2Gy group had low toxicity to the nude mice and no obvious side effects.In summary,we studied the anti-tumor effect of platinum complex,targeted ruthenium complexes and thermosensitive hydrogel.These research may provide new direction and theoretical basis for cancer treatment in the future.