Construction Of Platinum Drug Nano-delivery System And Its Anti-cancer Activity

With the high incidence of cancer in the world today,chemotherapy is one of the important means of clinical treatment.Platinum anticancer drugs account for 50%of the total clinical dosage.However,clinical platinum drugs have the problems of great toxicity and side effects and easily lead to drug resistance,which limits their further application.Therefore,the development of anticancer drugs and their new preparations is of great significance to the health of the whole people.The discovery of tetravalent platinum drugs and the nano-delivery of tetravalent platinum drugs have greatly improved the stability of platinum compounds and reduced toxic and side effects.There have been many studies on the nano-delivery of tetravalent platinum prodrugs.These delivery systems can not only extend the blood circulation time of drugs,but also improve the efficacy of drugs.Although many efforts to explore the delivery of tetravalent platinum prodrugs have been reported,the versatility of tetravalent platinum prodrugs has not been fully utilized,and because of the complex microenvironment at the tumor site,it is difficult to achieve good results with platinum drugs alone The therapeutic effect of combining two or more drugs to achieve the synergy of multiple treatment modes will be a new trend in cancer treatment.Photochemotherapy mainly includes photothermal therapy(PTT),photodynamic therapy(PDT).The combination of photothermal therapy and photodynamic therapy can synergistically anti-tumor effect.Based on these,this paper designed and synthesized different types of tetravalent platinum prodrugs,and examines in detail the versatility of platinum and the combined treatment effect.The research content is as follows:(1)Phenanthriplatin has a phenanthridine group ligand and exists in the form of a positive ion.It has high toxicity and broad-spectrum anticancer resistance,but its high toxicity limits its further clinical application.In order to solve the problem of high toxicity of phenanthridine platinum,this subject designed and synthesized a tetravalent phenanthridine platinum prodrug containing a long fat chain in the axial direction,and further assembled into a nanoparticle with a polymer having a carboxyl group in the side chain.The nanoparticles have reduction sensitivity and can release drugs responsively at the tumor site.In vitro and in vivo animal experiments have shown that the nanoparticles can effectively kill tumor cells.(2)As a classic anti-malarial drug,artesunate is also used in the treatment of cancer.Its mechanism of action is the cleavage of peroxygen bridge bonds,which generates(reactive oxygen species,ROS)and increases oxidative stress.The artesunate-modified tetravalent platinum prodrug Art-Pt was prepared and self-assembled with IR1048 into nanoparticles HSA@Art-Pt@IR assisted by human serum albumin.Under infrared laser irradiation,the nanoparticles increase the temperature of the tumor microenvironment and release ROS at high temperatures,enhancing the toxicity of cisplatin and synergistically improving the efficacy with platinum drugs.