Preparation Of Functional Hyperbranched Polyurethane Nanogels For Anticancer Drug Delivery

Chemotherapy plays an important role in the treatment of various malignant tumors today.However,the further clinical application was greatly limited due to the poor targeting,short circulation time,drug resistance and obvious systemic toxicity of small molecule chemotherapeutic drugs.In recent years,the development of nanotechnology has provided an effective way to improve the mode of delivery of chemotherapeutic drugs,reduce toxicity and side effects,and enhance therapeutic effect.Despite nanogelbased drug delivery systems owned obviously advantages for improving drug delivery efficiency compared to other nano-carriers,complicated preparation progress remains a challenge for their further application.Herein,a type of reduction responsive hyperbranched polyurethane nanogels(RSCS-PUNGs)with hydrophilic mPEG shell were prepared by a one-pot synthetic method in this work.The obtained RS-CS-PUNGs not only showed a narrow size distribution with the ideal hydrodynamic radii which around of 20 ± 3.0 nm,but also exhibited smart glutathione(GSH)responsive swelling property in PBS.Furthermore,doxorubicin(DOX)was used as a drug model.The drug release rate can be obviously enhanced with additional GSH(10 mM)compared to the control group which without disulfide bond(CS-PUNGs).Flow cytometric analysis and confocal laser scanning microscopy(CLSM)suggested that DOX-loaded RS-CSPUNGs could release the drug more quickly and show stronger intracellular fluorescence intensity than DOX-load CS-PUNGs.Furthermore,MTT assay indicated that the cytotoxicity of the DOX-loaded RS-CS-PUNGs showed a lower initial cytotoxicity compared to free DOX after treated 24 h,but could be obviously enhanced after treated 72 h compare with DOX-loaded CS-PUNGs,and there was no significant difference than free DOX.This RS-CS-PUNGs maybe hold the potential for their further application in the field of drug controlled release.