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Glyco-nanocarriers Based on Galac/Lactose Derivative for Targeted Drug Delivery

Zhichao Pei  Yingcheng Chang  Kui Yang  Yinghua Lv  Shoupeng Cao  Xiaowen Wu  Yuchao Lu  Yuxin Pei  
【摘要】:Glyco-nanocarriers including nano-vesicles and nano-rods based on amphiphilic pillar[5]arene and galactose derivatives for targeted drug delivery were developed.Firstly,glycolvesicles based on the host-guest complexation of pillar[5]arene and galactose derivative have been constructed,which showed GSH and pH responsiveness resulting from its ferrocenium cations or disulfide bond and ferrocenecarboxylic acid units respectively,where the cancer cells targetability was resulted from galactose units.Secondly,a novel drug delivery system based on supramolecular vesicles(TP5 G) self-assembled by the host–guest complex of tryptophan(Trp)-modified pillar[5]arene(TP5) and galactose derivative(G) has been developed,where TP5 can strongly interact with DNA in cells due to its Trp-rich structure.The vesicles can encapsulate DOX efficiently,and be used for controllable release in response to pH.Notably,DOX-loaded TP5 G exhibited significantly enhanced cytotoxicity compared to free DOX towards hepatoma cells through the synergistic effect of TP5 with DOX,resulting from the strong interactions between Trp-rich structure of TP5 and DNA in cells.Furthermore,DOX-loaded TP5 G showed unexpected ability to restore the drug sensitivity of DOX-resistant hepatoma cells(HepG2/ADR),which suggests TP5 G as a potential drug delivery system for overcoming multidrug resistance(MDR).Thirdly,a smart drug delivery system based on porous CeO2 nano-rods capped with galactose functionalized pillar[5]arene via host–guest interactions have been constructed,which showed GSH-responsiveness,synergistic anticancer of drugs and cancer target ability resulting from its disulphide unit,ceria properties and galactose unit,respectively.Moreover,the CeO2 nano-rods could be used not only as a drug carrier,but also as cancer cell-killing agent itself,which enhances anticancer efficiency in a synergistic manner.This report provides good examples for rationale design in the construction of multifunctional glyco-nanocarriers,which have great potential applications for cancer chemotherapies.

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