title: Dual photo- and pH-responsive supramolecular nanocarriers based on water-soluble pillar[6]arene and different azobenzene derivatives for intracellular anticancer drug delivery.
abstract: Two novel types of supramolecular nanocarriers fabricated by the amphiphilic host-guest inclusion complex formed from water-soluble pillar[6]arene (WP6) and azobenzene derivatives G1 or G2 have been developed, in which G1 is structurally similar to G2 but has an extra phenoxy group in its hydrophobic region. Supramolecular micelles can be initially formed by WP6 with G1, which gradually transform into layered structures with liquid-crystalline properties, whereas stable supramolecular vesicles are obtained from WP6 and G2, which exhibit dual photo- and pH-responsiveness. Notably, the resulting WP6⊃G2 vesicles can efficiently encapsulate anticancer drug mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which maintain good stability in a simulated normal physiological environment, whereas in an acid environment similar to that of tumor cells or with external UV irradiation, the encapsulated drug is promptly released. More importantly, cytotoxicity assay indicates that such vesicles have good biocompatibility and the MTZ-loaded vesicles exhibit comparable anticancer activity to free MTZ, especially with additional UV stimulus, whereas its cytotoxicity for normal cells was remarkably reduced. Flow cytometric analysis further confirms that the cancer cell death caused by MTZ-loaded vesicles is associated with apoptosis. Therefore, the dual pH- and UV-responsive supramolecular vesicles are a potential platform for controlled release and targeted anticancer drug delivery.
authors.affiliation: Key Laboratory of Mesoscopic Chemistry of MOE, Center for Multimolecular Organic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China).
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Hu
authors.forename: Keke
authors.initials: K
authors.lastname: Jia
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Qin
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Leyong
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001391:Azo Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D008942:Mitoxantrone / Q000737:chemistry / Q000633:toxicity; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001391:Azo Compounds; D004337:Drug Carriers; D008823:Micelles; D000644:Quaternary Ammonium Compounds; C581440:pillar(6)arene; D014867:Water; D008942:Mitoxantrone; C009850:azobenzene
keywords: drug delivery; micelles; pillararenes; supramolecular chemistry; vesicles