title: Poly(L-aspartamide)-based reduction-sensitive micelles as nanocarriers to improve doxorubicin content in cell nuclei and to enhance antitumor activity.
abstract: A reduction-sensitive graft polymer PHEA-S-S-C16 with poly{α,β-[N-(2-hydroxyethyl)-L-aspartamide]} (PHEA) as a backbone and a disulfide-containing alkyl as a side chain (HOOC-S-S-C16 ) is synthesized and evaluated for intracellular DOX delivery. PHEA-S-S-C16 can self-assemble into micelles in aqueous media and load DOX at a total content of 7.3%. In vitro release studies reveal that the release rate of DOX from PHEA-S-S-C16 micelles is accelerated in the presence of DTT. The results of cell experiments indicate that DOX-loaded mPEG-S-S-C16 micelles can achieve rapid DOX release in HeLa cells, as compared with their reduction-insensitive counterparts. Endocytosis inhibition analysis indicates that PHEA-S-S-C16 micelles entered cells mainly via clathrin-mediated endocytosis.
authors.affiliation: Department of Chemistry, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, China.
authors.forename: Can
authors.initials: C
authors.lastname: Cui
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Xue
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Huang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000502:physiology; D002966:Clathrin / Q000378:metabolism; D004229:Dithiothreitol / Q000737:chemistry; D004317:Doxorubicin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis*; D004705:Endocytosis / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D002966:Clathrin; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D004317:Doxorubicin; D004229:Dithiothreitol
keywords: drug delivery systems; micelles; nuclei; reduction-sensitive