A sulfur dioxide polymer prodrug showing combined effect with doxorubicin in combating subcutaneous and metastatic melanoma

查看全文 作　　者：Lin [1]An;Peng [2,3]Zhang;Wei [2]Shen;Xuan [2,3]Yi;Weitian [1]Yin;Rihua [1]Jiang;Chunsheng [2,3]Xiao

机构地区：[1]Department of Hand Surgery and Department of Dermatology,China-Japan Union Hospital of Jilin University,Changchun,130033,PR China;[2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun,130022,PR China;[3]Jilin Biomedical Polymers Engineering Laboratory,Changchun,130022,PR China

出　　处：《Bioactive Materials》索引2021年第6卷第5期,共10页

基　　金：supported by the National Natural Science Foundation of China(51803209,51773196,and 51573184);the Jilin Provincial Science and Technology Development Program(20190201205JC,20190103022JH,and 20190103038JH);the Youth Innovation Promotion Association of Chinese Academy and Sciences(2017266). 摘　　要：Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the patient survival rate.Therefore,early treatment of the melanoma in situ or timely blocking the deterioration of metastases is critical.In this study,a sulfur dioxide(SO_(2))polymer prodrug was designed as both an intracellular glutathione(GSH)-responsive SO_(2) generator and a carrier of doxorubicin(DOX),and used for the treatment of subcutaneous and metastatic melanoma.Firstly,chemical conjugation of 4-N-(2,4-dinitrobenzenesulfonyl)-imino-1-butyric acid(DIBA)onto the side chains of methoxy poly(ethylene glycol)grafted dextran(mPEG-g-Dex)resulted in the synthesis of the amphiphilic polymer prodrug of SO_(2),mPEG-g-Dex(DIBA).The obtained mPEG-g-Dex(DIBA)could self-assemble into stable micellar nanoparticles and exhibited a glutathione-responsive SO_(2) release behavior.Subsequently,DOX was encapsulated into the core of mPEG-g-Dex(DIBA)micelles to form DOX-loaded nanoparticles(PDDN-DOX).The formed PDDN-DOX could be internalized by B16F10 cells and synchronously release DOX and SO_(2) into the tumor cells.As a result,PDDN-DOX exerted synergistic anti-tumor effects in B16F10 melanoma cells because of the oxidative damage properties of SO_(2) and toxic effects of DOX.Furthermore,in vivo experiments verified that PDDN-DOX had great potential for the treatment of subcutaneous and metastasis melanoma.Collectively,our present work demonstrates that the combination of SO_(2)-based gas therapy and chemotherapeutics offers a new avenue for inhibiting melanoma progression and metastases. 关键词：Glutathione-responsive Melanoma Polymer prodrug Sulfur dioxide

相关文献

参考文献（57）
引证文献（4）
耦合文献（26）

参考文献(57)

引证文献(4)

耦合文献(26)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

A sulfur dioxide polymer prodrug showing combined effect with doxorubicin in combating subcutaneous and metastatic melanoma

参考文献(57)

引证文献(4)

耦合文献(26)

用户提示