Based on specific host-guest interactions between amine-modified ?-cyclodextrin(CD-TAEA) and functional adamantane(AD) derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assemblies 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 consideration 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 microscopy and flow cytometry experiments demonstrated the important contribution of the functional PB-AD module to the considerably enhanced intracellular internalization and uptake by cellular nuclei. Compared to the parent CD-TAEA, PB-AD/CDTAEA assemblies mediated higher transfection rates, which were even comparable to that of PEI25K. In addition, PB-AD/CDTAEA 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. Based on specific host-guest interactions between amine-modified? -cyclodextrin (CD-TAEA) and functional adamantane (AD) derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assemblies 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 consideration 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 microscopy and flow cytometry experiments presented in the important contribution of the functional PB-AD module to the substantial enhanced intracell In addition, PB-AD / CDTAEA exhibited 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.