title: Star-shape redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol-lysine-di-tocopherol succinate for tumor-triggering intracellular doxorubicin rapid release: head-to-head comparison.
abstract: A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P(5k)SSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P(5k)LV (P(5k)LV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P(5k)SSLV-DOX, P(5k)LV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P(5k)SSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P(5k)LV-DOX nanomicelles. In conclusion, the redox-responsive P(5k)SSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, P. R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ai
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Zhong
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Wu
authors.forename: Handong
authors.initials: H
authors.lastname: Niu
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: He
authors.initials: H
authors.lastname: Lian
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Han
authors.forename: Guolian
authors.initials: G
authors.lastname: Ren
authors.forename: Wenya
authors.initials: W
authors.lastname: Ding
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Pu
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D004339:Drug Compounding; D019008:Drug Resistance, Neoplasm; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D014810:Vitamin E; D011092:Polyethylene Glycols; D004317:Doxorubicin; C014225:tocophersolan
keywords: Doxorubicin; intracellular drug release; nanomicelles; redox-responsive; vitamin E succinate