title: Pillar[5]arene-based amphiphilic supramolecular brush copolymer: fabrication, controllable self-assembly and application in self-imaging targeted drug delivery.
abstract: Supramolecular brush copolymers have attracted continuing interest due to their unusual architectures, fascinating properties, and potential applications in many fields involving smart stimuli-responsive drug delivery systems. Herein, the first pillararene-based amphiphilic supramolecular brush copolymer (P5-PEG-Biotin⊃PTPE) was constructed on the basis of the host-guest molecular recognition between a water-soluble pillar[5]arene (P5) and a viologen salt (M).P5-PEG-Biotin⊃PTPEself-assembled into supramolecular nanoparticles (SNPs), which were utilized as a self-imaging drug delivery vehicle by taking advantage of the aggregation-induced emission (AIE) effect. Encapsulation of anticancer drug doxorubicin (DOX) caused deactivation of the fluorescences of both the tetraphenylethene (TPE) and DOX chromophores due to the energy transfer relay (ETR) effect, mediated by Förster resonance energy transfer (FRET) and aggregation-caused quenching (ACQ). The release of loaded DOX molecules can be triggered by low pH and reductase, recovering the "silenced" fluorescence caused by the interruption of the ETR effect, achievingin situvisualization of the drug release process by observing the location and magnitude of the energy transfer-dependent fluorescence variation. The biotin ligands on the surfaces of the DOX-loadedSNPsact as targeting agents to deliver DOX preferentially to cancer cells over-expressing biotin receptor.In vitrostudies demonstrated that the loading of DOX by this supramolecular nanomaterial exhibited selective cytotoxicity towards cancer cells over normal cells. The potency of this sophisticated supramolecular drug delivery system in cancer therapy was further evaluated in HeLa tumor-bearing mice.In vivoexperiments confirmed that the DOX-loadedSNPspossess excellent antitumor efficacy with negligible systemic toxicity.
authors: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors: Guocan
authors: G
authors: Yu
authors: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Run
authors: R
authors: Zhao
authors: Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Dan
authors: D
authors: Wu
authors: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors: Fuwu
authors: F
authors: Zhang
authors: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Li
authors: L
authors: Shao
authors: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Jiong
authors: J
authors: Zhou
authors: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Jie
authors: J
authors: Yang
authors: Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Guping
authors: G
authors: Tang
authors: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors: Xiaoyuan
authors: X
authors: Chen
authors: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
authors: Feihe
authors: F
authors: Huang