Based on specific host-guest interactions between amine-modified [3-cyclodextrin （CD-TAEA） and functional adamantane （AD） derivatives, a module-template strategy has been proposed for the construction of low-molec...Based on specific host-guest interactions between amine-modified [3-cyclodextrin （CD-TAEA） and functional adamantane （AD） derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assem- blies for gene transport. This strategy offers great flexibility in terms of the introduction of mono- or multi-functionality by the inclusion of one or more adamantane-based modules with the desired functionalities. As proof of concept, phenylboronic acid （PB） containing adamantane （PB-AD） was used as a model module in the hope of offering enhanced cytosolic delivery in con- sideration of the special affinity of PB groups with cell membranes. The physicochemical properties of the complexes formed with plasmid DNA, such as particle size, zeta potential and morphology were investigated. Confocal laser scanning microsco- py and flow cytometry experiments demonstrated the important contribution of the functional PB-AD module to the consider- ably enhanced intracellular internalization and uptake by cellular nuclei. Compared to the parent CD-TAEA, PB-AD/CD- TAEA assemblies mediated higher transfection rates, which were even comparable to that of PEI25K. In addition, PB-AD/CD- TAEA displayed much lower cytotoxicity than PEI25K in both 293T and HeLa cell lines. The encouraging results suggest that CD-TAEA can be developed as a powerful template capable of readily accommodating various AD-based modules giving versatile functionalities for improved transfection.展开更多
基金supported by the National Basic Research Program of China(2011CB606202)the National Natural Science Foundation of China(21174110)+1 种基金the Ministry of Education of China(20120141130003)the Fundamental Research Funds for the Central Universities(2012203020210)
文摘Based on specific host-guest interactions between amine-modified [3-cyclodextrin （CD-TAEA） and functional adamantane （AD） derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assem- blies for gene transport. This strategy offers great flexibility in terms of the introduction of mono- or multi-functionality by the inclusion of one or more adamantane-based modules with the desired functionalities. As proof of concept, phenylboronic acid （PB） containing adamantane （PB-AD） was used as a model module in the hope of offering enhanced cytosolic delivery in con- sideration of the special affinity of PB groups with cell membranes. The physicochemical properties of the complexes formed with plasmid DNA, such as particle size, zeta potential and morphology were investigated. Confocal laser scanning microsco- py and flow cytometry experiments demonstrated the important contribution of the functional PB-AD module to the consider- ably enhanced intracellular internalization and uptake by cellular nuclei. Compared to the parent CD-TAEA, PB-AD/CD- TAEA assemblies mediated higher transfection rates, which were even comparable to that of PEI25K. In addition, PB-AD/CD- TAEA displayed much lower cytotoxicity than PEI25K in both 293T and HeLa cell lines. The encouraging results suggest that CD-TAEA can be developed as a powerful template capable of readily accommodating various AD-based modules giving versatile functionalities for improved transfection.
