Redox-responsive Ditelluride-containing Poly (Ether-urethane) Nanoparticles For Controlled Drug Release

ObjectiveWith the development of modern medicine,the chemical treatment of cytotoxic drugs becomes an important mean of antitumor treatments,while the poor selectivity of small molecule cytotoxic drugs causes damage to normal tissues and cells,which is a big obstacle to its clinical application.In this study,we are committed to fabricate redox-responsive ditelluride-containing poly(ether-urethane)nanoparticles,which can be used to encapsulate hydrophobic doxorubicin(DOX),a representative clinical antitumor drug.The rapidly responsive drug delivery system is developed to protect DOX from being released in the process of in vivo transport and make the controlled and tumor-targeting release possible,and improve the antitumor effect of the drug.MethodsIn this study,the amphiphilic copolymer PEG-PUTeTe-PEG was synthesized via facile one-pot approach.And the copolymer was used as material to prepare the DOX-loaded PEG-PUTeTe-PEG nanoparticles(named Te-DOX for short).Then the stability,the reduction response,the behavior of in vitro drug release and the biological distribution of Te-DOX was further investigated via a series of experiments.And finally,in vivo antitumor activity of Te-DOX was monitored.ResultsThe synthesis of drug-loaded redox-responsive ditelluride-containing poly(ether-urethane)nanoparticles is successful.And ditelluride bones were introduced into water-soluble polymers for the first time in the field of polymer chemistry.Drug-loaded nanoparticles accumulate in solid tumor parts via enhanced permeation and retention effect(EPR effect)and can be endocytosed into the cells.The ditelluride bonds of drug carriers can be rapidly cleaved by GSH,a reducing reagent in cells,which leads to the dissociation of nanoparticles.This process can make the release of encapsulated drugs much more controllable.The responsive drug delivery system mentioned in this study shows excellent chemical stability and biocompatibility,and has significant antitumor activity against solid tumor.ConclusionIn a conclusion,a redox-responsive system for the controlled drug release was fabricated by ditelluride-containing poly(ether-urethane)compolymers.At the same time,these in vitro and in vivo studies suggest that the drug-loaded ditelluride-containing poly(ether-urethane)nanoparticles exhibit excellent tumor targeting ability and antitumor activity,which have great potential of targeted chemotherapy for cancer.This study may enrich the family of delivery systems and provide a new platform for future biomedical nanotechnologies.