Effects of organic solvents on the structures of micellar nanocrystals

Micellar nanocrystals (nanocrystal-encapsulated micelles) has become an emerging class of nanomaterials for a wide spectrum of biomedical applications. The most commonly used approach to vary the properties of micellar nanocrystals is using different types or molecular weights of amphiphilic molecules. The present work focuses on investigating the effects of an alternative material parameter, i.e., organic solvent, which primarily affects the kinetics rather than thermodynamics of the formation process, on the structures of the micellar nanocrystal product fabricated by combining electrospray and self-assembly. We find that, compared with chloroform (commonly used in prior works and used as the reference here) as the organic solvent, dichloromethane (DCM, lower boiling point than chloroform) leads to nearly zero encapsulation of nanocrystals in micelles, and tetrahydrofuran (THF, higher water miscibility than chloroform) leads to greatly enhanced encapsulation of nanocrystals in micelles. The use of THF could thus solve the previously identified problem of low nanocrystal encapsulation. Surprisingly, a prolonged fabrication process of micellar nanocrystals with THF is found to generate worm-shaped products. Further study of the formation mechanism of the worm-shaped micelles indicates that they are formed through THF-induced/facilitated fusion of spherical micelles. The thus-formed worm-shaped micellar nanocrystals are found to offer greatly reduced non-specific cellular uptake than the spherical counterparts. These results offer significant insights on micellar nanocrystal, micelle fusion as well as self-assembly, and provide new ways to control the structures of nanomaterials and their biological responses.