摘要
Chemotherapy is one of the most conventional modalities for cancer therapy.However,the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy.Considering the ability of nitric oxide(NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance,a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy.Herein,a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin(DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment.The micelle consists of DOX as core,arginine/glucose oxidase(Arg/GOx) as shell and redox-responsive disulfide bond as a linker,which is denoted as micelle-DOX-Arg-GOx.The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide(H_(2) O_(2)) for increasing the generation of NO.Moreover,the glucose supply could be simultaneously blocked by the catalytic process,which further enhanced therapeutic efficiency.This micelle requests a tumor-specific microenvironment(a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy,starvation therapy(catalytic medicine),and gas therapy for tumor treatment,which resulted in significant cytotoxicity to tumor tissue.
基金
supported by the National Natural Science Foundation of China (No.81601606to Xin Chen)
the"Young Talent Support Plan"of Xi’an Jiaotong University (Xin Chen)
the Technology Foundation for Selected Overseas Chinese Scholar of Shaanxi Province (Xin Chen)
the Fundamental Research Funds for the Central Universities (No.2016qngz02 to Xin Chen)
the One Hundred Talents Program of Shaanxi Province (Xin Chen)
National Natural Science Foundation of Shaanxi Province (No.2017JM5023to Xin Chen)
open fund of the State Key Laboratory of Military Stomatology (No.2017KA02 to Xin Chen)
the Knowledge Innovation Program of Shenzhen (No.JCYJ20170816100941258to Xin Chen)
Beijing Nova Program of Science and Technology (No.Z191100001119096 to Zhongning Liu)。