Stimuli-responsive lyotropic liquid crystalline nanoparticles: adaptive soft matter in action

Lyotropic liquid crystalline nanoparticles (LLCNPs) such as cubosomes and hexosomes have emerged as versatile nanocarriers for the delivery of bioactive agents due to their tunable internal structures, high surface area, and ability to encapsulate hydrophilic, hydrophobic, and amphiphilic cargos. Lipid nanoparticles self-assembled from amphiphilic lipids, such as monoolein and phytantriol, or their polymer analogs, form ordered mesophases whose curvature and lattice parameters can be modulated through composition. The unique internal nanostructures of LLCNPs critically influence their physicochemical properties, which in turn affect cellular uptake mechanisms and drug release profiles. Stimuli-responsiveness – pH, enzymatic activity, temperature, ionic strength, magnetic field, oxidation, and light – can be engineered by incorporating ionizable lipids, phospholipids, responsive polymers, or photosensitive molecules, enabling controlled and on-demand release. Moreover, hybrid systems incorporating magnetic or polymeric components further expand LLCNPs functionality. This review provides a comprehensive overview of the design principles and stimuli-responsive behavior of cubosomes and hexosomes, emphasizing their potential for precision drug delivery.