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Cascade Amplifiers Of Intracellular Reactive Oxygen Species Based On Mitochondria-targeted Core-shell ZnO-TPP@D/H Nanorods For Breast Cancer Therapy

Posted on:2020-12-24Degree:MasterType:Thesis
Country:ChinaCandidate:X LiangFull Text:PDF
GTID:2404330620960581Subject:Pharmacy
Abstract/Summary:
Tumor cells are vulnerable to reactive oxygen species(ROS).However,it is still a challenge to induce ROS efficiently in tumor cells.In this study,cascade amplifiers of intracellular ROS based on charge-reversible mitochondria-targeted ZnO-TPP@D/H nanorods were first developed for breast cancer therapy.The core-shell ZnO-TPP@D/H NR with a particle size of 179.60 ± 5.67 nm was composed of a core of a ZnO NR,an inner shell of triphenyl phosphonium(TPP),and an outer shell of heparin.Doxorubicin(DOX)was loaded on ZnO-TPP@D/H NRs with high drug loading efficiency of 21.70 ± 1.80%.The zeta potential of ZnO-TPP@D/H NRs varied from 37.03 ± 2.04 to-34.06 ± 0.87 mV after heparin coating,protecting ZnO-TPP@D/H NRs from nonspecific adsorption in circulation.Mitochondrial targeting was achieved after the degradation of heparin.Cellular uptake assays showed that ZnO-TPP@D/H NRs could amplify the intracellular ROS in 4T1 cells(highly metastatic breast cancer cells)than free DOX.Western blot demonstrated that ZnO-TPP@D/H NRs dramatically induced cell apoptosis in 4T1 cells.In vivo experiments suggested the anti-tumor potential of ZnO-TPP@D/H NRs.
Keywords/Search Tags:breast cancer, mitochondrial targeting, reactive oxygen species, nanorods, zinc oxide
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