Controlling Complex Stability in Photoresponsive Macromolecular Host-Guest Systems: Toward Reversible Capture of DNA...

An effective and universal method for delivering structurally diverse biomolecules in vivo would greatly benefit modern drug therapy, but has yet to be discovered. Self-assembled supramolecular complexes containing vesicles of amphiphilic cyclodextrin and linker molecules with an azobenzene guest unit and a charged functionality have been established as nanoscale carriers for proteins and DNA, making use of multivalent electrostatic attraction. However, light-induced cargo release is only feasible up to a maximum net charge of the biomacromolecules. Herein, it is shown that it is possible to fine-tune macromolecular complex stability and size by addition of a competitive guest molecule that acts as a stopper, partly blocking the vesicle surface. The superior performance of arylazopyrazoles in photoisomerization compared to azobenzenes, which enables a lower surface charge density of the vesicles in the photostationary state, is also demonstrated. Both strategies allow reversible supramolecular aggregation of high molecular weight DNA (2 and 4.8 kbp).