Hydrogen‐Bonding‐Regulated Supramolecular Nanostructures and Impact on Multivalent Binding

Herein we describe the H‐bonding‐regulated nanostructure, thermodynamics, and multivalent binding of two bolaamphiphiles NDI‐1 and NDI‐2 consisting of a hydrophobic naphthalene diimide connected to a hydrophilic wedge by a H‐bonding group and a glucose moiety on its two arms. NDI‐1 and NDI‐2 differ by the single H‐bonding group, namely, hydrazide or amide, which triggers the formation of vesicles and cylindrical micelles, respectively. Although the extended H‐bonding ensures stacking with head‐to‐head orientation and the formation of an array of the appended glucose moieties in both systems, the adaptive cylindrical structure exhibited superior multivalent binding with concanavalin A (ConA) to that of the vesicle. A control amphiphile lacking a H‐bonding group assembled with a random lateral orientation to produce spherical micelles without any notable multivalent binding.     

The siRNAsome: A Cation‐Free and Versatile Nanostructure for siRNA and Drug Co‐delivery

Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs together with the co‐delivery of siRNAs, which avoid the problem of cation‐associated cytotoxicity, are lacking. Herein, we report an small interfering RNA (siRNA)‐based vesicle (siRNAsome), which consists of a hydrophilic siRNA shell, a thermal‐ and intracellular‐reduction‐sensitive hydrophobic median layer, and an empty aqueous interior that meets this need. The siRNAsome can serve as a versatile nanostructure to load drug agents with divergent chemical properties, therapeutic proteins as well as co‐delivering immobilized siRNAs without transfection agents. Importantly, the inherent thermal/reduction‐responsiveness enables controlled drug loading and release. When siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride and anti‐P‐glycoprotein siRNA, synergistic therapeutic activity is achieved in multidrug resistant cancer cells and a tumor model.