Metal Ion (Fe and Co) Induced Morphological Transformation of Self-Aggregates of Cholesterol-Tethered Bipyridine Amphiphiles: Selective Cancer Cell Killing by Pro-Drug Activation.

Design and development of diverse supramolecular self-assemblies from a single amphiphilic molecule has always been challenging, and it can have prospects in different task-specific applications. The present study reports the formation of different morphologies of self-aggregates by the inclusion of transition metals that are biologically more relevant due to their participation in biochemical reactions. A cholesterol-tethered bipyridine-appended amphiphile (CBB) has been synthesized that spontaneously formed vesicles in a 2:1 DMSO-water (v/v) solvent mixture. This vesicle undergoes metal-ion-induced transition from the vesicle to associated vesicles or sheets. The formation of the associated vesicular structure was observed in the presence of a transition metal ion, Fe, while morphological transformation from the vesicle to sheet took place in the presence of Co. Different spectroscopic and microscopic investigations showed that both the morphological transformations took place via the alteration of the molecular-level aggregation pattern from -type (for vesicle formed by only CBB) to -type (for the associated vesicle or sheet formed by metal ion included CBB). Moreover, the Fe-containing self-aggregate successfully produced reactive oxygen species (ROS, i.e., hydroxyl/superoxide radicals) from HO through Fenton reactions. This unique characteristic of Fe including a self-aggregate was utilized for oxidative DNA damage in the presence of HO. Consequently, this Fe(II)-CBB complex self-aggregate was exploited in selective and efficient killing of cancer cells owing to its high HO content. Thus, Fe(II)-included self-assembly (associated vesicular aggregate) of CBB becomes the unique pro-drug activator which can selectively destroy the cancer cells through Fenton reaction even in the absence of any anticancer drug.