Controllable Construction of Biocompatible Supramolecular Micelles and Vesicles by Water-Soluble Phosphate Pillar[5,6]arenes for Selective Anti-Cancer Drug Delivery

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• 作者：Xiao-Yu Hu ; Xin Liu ; Wenyi Zhang ; Shan Qin ; Chenhao Yao ; Yan Li ; Derong Cao ; Luming Peng ; Leyong Wang
• 刊名：Chemistry of Materials
• 出版年：2016
• 出版时间：June 14, 2016
• 年：2016
• 卷：28
• 期：11
• 页码：3778-3788
• 全文大小：693K
• 年卷期：0
• ISSN：1520-5002

文摘

The controllable construction of biocompatible supramolecular nanocarriers with different morphologies based on dynamic noncovalent interactions to achieve selective delivery of drugs with different properties remains highly challenging. We herein report controllable construction of two types of supramolecular nanocarriers based on biocompatible water-soluble phosphate-based pillar[5]arene (WP5P) or pillar[6]arene (WP6P) with pyridinium bromide guest G for the selective anticancer drug delivery. Solid supramolecular micelles could be obtained by the amphiphilic host–guest inclusion complex formed from WP5P and G, whereas hollow supramolecular vesicles were acquired from WP6P and G. Both of them showed pH- and Zn²⁺-responsiveness. Furthermore, the resulting solid micelles were able to encapsulate hydrophobic anticancer drug doxorubicin (DOX) to achieve DOX-loaded micelles, while hydrophilic anticancer drug mitoxantrone (MTZ) could be successfully loaded into the hollow vesicles. Additionally, the encapsulated anticancer drugs could be efficiently released at low-pH environment or with the introduction of Zn²⁺. More importantly, cytotoxicity experiments indicated that these water-soluble phosphate-based pillar[5,6]arenes showed excellent biocompatibility, and the drug-loaded nanoparticles exhibited comparable therapeutic effect for cancer cells as free anticancer drugs and remarkably reduced damage for normal cells as well. Cellular uptake and intracellular localization experiments further confirmed that these two types of nanocarriers, taken up by cancer cells via endocytosis, could lead to efficient drug accumulation in cancer cells. Therefore, this strategy of controllable construction of different types of stimuli-responsive supramolecular nanocarriers based on biocompatible phosphate-based pillar[5,6]arenes have great potential applications in the field of controlled drug delivery.