In this research, we successfully performed a "click" synthesis of amphiphilic poly(amido amine) dendron-bearing fullerenyl conjugate (C60 G1 ) using a copper(I)-catalyzed azide-alkyne cycloaddition reaction. The strong hydrophobicity of the C60 moiety induces self-assembly of C60 G1 into core-shell-like "pseudodendrimers" with a uniform size distribution and positively charged peripherals. The pseudodendrimers were well-characterized by atomic force microscopy (AFM), transmission electron microscopy, and dynamic light scattering. On the basis of electrostatic interactions, the polycationic C60 G1 assembly can serve as a nonviral gene vector. An ethidium bromide displacement assay and agarose gel electrophoresis both indicated that C60 G1 assembly forms stable complexes with the cyclic reporter gene (pEGFP-C1) at low nitrogen-to-phosphorous (N/P) ratios. AFM analysis revealed a dynamic complex-formation process, and confirmed the synthesis of C60 G1 /pEGFP-C1 hybrids with a particle dimensions less than 200 nm. Fluorescence microscopy and flow cytometry revealed that 51% of HeLa and 43% of MCF-7 cells are positive to the YOYO-1-labeled hybrids at an N/P ratio of 2, being comparable to TurboFect-mediated delivery.
Keywords: PAMAM dendrimer; amphiphilic dendrons; click chemistry; fullerene; gene delivery.
© 2014 Wiley Periodicals, Inc.