Pillar[5]arene-based amphiphilic supramolecular brush copolymers: fabrication, controllable self-assembly and application in self-imaging targeted drug delivery

被引：127

作者：

Yu, Guocan ^{[1
,3
]}

Zhao, Run ^{[1
]}

Wu, Dan ^{[2
]}

Zhang, Fuwu ^{[3
]}

Shao, Li ^{[1
]}

Zhou, Jiong ^{[1
]}

Yang, Jie ^{[1
]}

Tang, Guping ^{[2
]}

Chen, Xiaoyuan ^{[3
]}

Huang, Feihe ^{[1
]}

机构：

[1] Zhejiang Univ, Dept Chem, Ctr Chem High Performance & Novel Mat, State Key Lab Chem Engn, Hangzhou 310027, Peoples R China

[2] Zhejiang Univ, Dept Chem, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310027, Peoples R China

[3] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA

来源：

POLYMER CHEMISTRY | 2016年 / 7卷 / 40期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

MOLECULAR RECOGNITION; POLYMER BRUSHES; POLYPRODRUG AMPHIPHILES; CANCER-THERAPY; NANOPARTICLES; WATER; RELEASE; DESIGN; MICELLES; COMBINATION;

D O I：

10.1039/c6py01402j

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

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 superset of 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 superset of PTPE self-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 fluorescence of both the tetraphenylethene (TPE) and DOX chromophores due to the energy transfer relay (ETR) effect, mediated by Forster 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, achieving in situ visualization 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-loaded SNPs act as targeting agents to deliver DOX preferentially to cancer cells over-expressing biotin receptors. In vitro studies 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 tumorbearing mice. In vivo experiments confirmed that the DOX-loaded SNPs possess excellent antitumor efficacy with negligible systemic toxicity.

引用

页码：6178 / 6188

页数：11

共 98 条

[91] Pillar[6]arene/Paraquat Molecular Recognition in Water: High Binding Strength, pH-Responsiveness, and Application in Controllable Self-Assembly, Controlled Release, and Treatment of Paraquat Poisoning [J].