A Molecular Umbrella Approach to the Intracellular Delivery of siRNA

A series of diwalled and tetrawalled molecular umbrellas have been synthesized using cholic acid, spermidine, and lysine as starting material. Coupling of these molecular umbrellas to an octaarginine peptide afforded agents that were capable of promoting the transport of small interfering RNA (siRNA) to HeLa cells, as judged by the knockdown of enhanced green fluorescent protein (eGFP) expression. The efficiency of this knockdown was found to increase with an increasing number of facially amphiphilic walls present, and also when a cleavable disulfide linker was replaced with a non-cleavable, maleimido moiety. The knockdown efficiency that was observed for one tetrawalled molecular umbrella-octaargine conjugate was comparable to that observed with a commercially available transfection agent, Lipofectamine 2000, but showed less cytotoxicity

Minimizing Defects in Polymer-Based Langmuir–Blodgett Monolayers and Bilayers via Gluing

Polymeric surfactants were prepared by quaternization of poly­(4-chloromethylstyrene) with <i>N</i>,<i>N</i>-dimethyl-<i>N</i>-<i>n</i>-dodecylamine and <i>N</i>,<i>N</i>-dimethyl-<i>N</i>-<i>n</i>-octylamine to give <b>1</b> and <b>2</b>, respectively. Each of these polymers formed stable monolayers at the air/water interface. Injection of poly­(acrylic acid) (PAA) beneath the surface of these films led to a substantial increase in their cohesiveness (i.e., “gluing”), as evidenced by a dramatic increase in their surface viscosity. Examination of monolayers of <b>1</b> by atomic force microscopy, after being transferred to silicon wafers that were surface-modified with <i>n</i>-octadecyltrichlorosilane, showed that the presence of PAA leads to intact film. In contrast, transfer of unglued monolayers resulted in poor coverage. Comparison of the barrier properties of single glued and unglued LB bilayers formed in the presence and in the absence of PAA have shown that PAA minimizes defect formation within these ultrathin assemblies