Design And Synthesis Of ROS-Responsive Intelligent Drug Delivery System

Cancer is one of the biggest killers threatening human life all over the world and and it is a major challenge in the current medical research field.Chemotherapy is one of the most familiar cancer treatments that can destroy and eliminate cancer cells by anticancer drugs.Due to the drug resistance and chemical toxicity of chemotherapy,single-function chemotherapy has not been enough to meet the needs of cancer treatment.In this regard,it seems to be a good choice to design a multifunctional nano-drug delivery system that can effectively overcome multi-drug resistance in chemotherapy.A large amount of evidences show that:due to the lack of antioxidant enzymes,cancer cells lack sufficient ROS scavenging ability to maintain the Redox homeostasis,which leads to cancer cells having higher levels of reactive oxygen species(ROS)compared with normal somatic cells.Based on the physiological changes of ROS abnormal increase in the disease site,on the one hand,by taking advantage of high levels of reactive oxygen species in tumor tissues,an intelligent nano-drug delivery system with targeted ROS stimulation response could be designed for cancer specific treatment.On the other hand,excessive accumulation of high active ROS in cancer cells can form oxidative stress,which can lead to oxidation of proteins and nucleic acids,DNA damage,and even cell death.On this basis,if a multifunctional nano-drug delivery system can be designed,on the one hand,a large amount of accumulated ROS at the tumor tissue can be utilized to achieve a stimulus response and release the encapsulated anticancer drug.On the other hand,it is also possible to destroy the intracellular redox homeostasis by promoting ROS production or reducing ROS scavengers,thereby effectively amplifying oxidative stress in cells,and performing oxidative treatment of tumors.Then the therapeutic mechanism that combines chemotherapy with oxidative therapy will overcome multidrug resistance and improve the therapeutic effect of the tumor.Based on the above ideas,we put forward the following schemes:(1)We synthesized a kind of ROS-stimulated responsive nano-drug delivery system using a material which contains phenylboronic acid pinacol ester.When exposed to the overexpression ROS environment in tumor tissues,the phenylboronic acid pinacol ester bond of the ROS-stimulated responsive nano-drug delivery system is broken,and the nanoparticles are degraded into small molecules,which are accompanied by the precise delivery of anticancer drugs and the improved efficiency of chemotherapy.(2)Carboxyferrocene is grafted onto ROS-sensitive nanoparticles.A nano-drug delivery system which can realize the synergistic effect of chemotherapy and oxidation therapy was prepared.Under the ROS environment,the phenylboronic acid pinacol ester bond is broken,and the nanoparticles are degraded into small molecules to release anticancer drugs at the same time.In addition,when the carboxyferrocene is in contact with intracellular H2O2,it will convert hydrogen peroxide to hydroxyl radicals by Fenton reaction for the oxidation therapy,which can cause oxidative damages to lipids,proteins,and DNA and it can effectively kill cancer cells and inhibit tumor growth.Here,we can not only utilize ROS sensitive organosilicon nanoparticles to achieve precise release of anticancer drugs,but also make use of the carboxyferrocene grafted on organosilicon nanoparticles to induce tumor-site specific ROS transformation to generate hydroxyl radical(·OH),which enhances anticancer activity and minimizes systemic toxicity.This specific stimulation response mechanism is expected to achieve the synergistic effect of chemotherapy and oxidation therapy and is beneficial to achieve high-efficiency tumor treatment.