Spontaneous formation of a vesicular assembly by a trimesic acid based triple tailed amphiphile

Abstract

Trimesic acid based amino acid functionalized triple tailed amphiphiles (TMA-1 and TMA-2) were synthesized. The triskelion amphiphile TMA-1 with a neutral side chain self-assembled into a vesicle in 2:1 (v/v) DMSO–water, while the ammonium side chain decorated TMA-2 formed vesicles in pure water. Microscopic and spectroscopic characterizations were carried out to confirm the self-aggregated vesicular morphology and its size which is around 250–300 nm in the case of TMA-1 and around 100–150 nm for TMA-2 vesicles. The unique structure of these amphiphiles with an aromatic core and three hydrophilic side chains led to an interlamellar orientation of their hydrophobic (aromatic) domain, while hydrophilic terminals were directed toward the aqueous domain. These amphiphiles formed monolayered vesicles possibly through H-aggregation during the process of self-assembly, which is different from conventional bilayered vesicles formed by twin-chain lipid molecules. The time resolved decay curve of hydrophobic dye entrapped within these vesicles indicated that the hydrophobicity within the microenvironment of TMA-1 and TMA-2 vesicles is higher than that in pure water; however, at the same time, it is comparatively lower than that observed in bilayered phosphocholine vesicles. Furthermore, calcein dye was entrapped within these vesicles to ensure their encapsulation efficiency (65–85%). The ability to entrap dye molecules by these synthesized vesicles was utilized to encapsulate and deliver anticancer drug doxorubicin inside the mammalian cells. A simple synthetic procedure and facile aggregation to vesicular self-assembly with superior dye/drug encapsulation proficiency made these vesicles a potential cellular transporter.