Colloids and Surfaces B: Biointerfaces 116 (2014) 153–159 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Simple synthesis, self-assembly, and cytotoxicity of novel dimeric cholesterol derivatives Tzung-Han Chou a,∗ , Chien-Wen Chen a , Chia-Hua Liang b , Li-Hsien Yeh a , Shizhi Qian c a Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Yunlin 64002, Taiwan b Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan c Institute of Micro/Nanotechnology, Old Dominion University, Norfolk, VA 23529, USA article info Article history: Received 15 September 2013 Received in revised form 7 December 2013 Accepted 20 December 2013 Available online 31 December 2013 Keywords: Dimeric cholesteryl derivatives Self-assembly Nano-structural aggregates Cytotoxicity HaCaT cells abstract A simple and economic methodology to synthesize three types of novel dimeric cholesterol deriva- tives (DCDs) was developed. Results obtained from dynamic light scattering and transmission electron microscopy show that spherical and/or angular nano-structural aggregates of DCDs are formed by self- assembly in aqueous solution. The size and morphology of DCD dispersions depend on the spatial arrangement of the substituents and polarity of the head group in the DCD structures. The cytoxicity of DCD dispersions to human keratinocytes (HaCaT) and squamous cell carcinomas (SCC25) cells was also evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The present novel DCD dispersions were not toxic to HaCaT and SCC25 cells at appropriate tested concentrations. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved. 1. Introduction Molecular self-assembly is an incredibly powerful phenomenon in modern molecular science. Small or macro-molecules can aggre- gate into new or special structures with various functions under specific conditions through molecular self-assembly [1]. Over the past decade, molecular self-assembly has drawn significant atten- tions for its potential applications in many areas because of the possibility of forming micro- [2,3] or nano-scale [3–6] aggregates with special well-organized structures [6], morphology [7], and functions [8]. Self-assembly is driven mainly by molecular inter- actions, such as electrostatic interactions, van der Waals’ force, dipole interactions, hydrogen bonding, hydrophobic interactions, and – interactions [9]. Among them, hydrophobic interaction is the strongest driving force of the self-organization of amphiphilic molecules in water [9–11]. Molecular self-assemblies form vari- ous morphological transformations, which are determined by the structural conformation of aggregated molecules and the environ- mental conditions [9–11]. Cholesterol is one of the main constituents of cell membranes and has been considered to govern the membrane fluidity and permeability of the hydrophilic drug [11,12]. It was found that ∗ Corresponding author. Tel.: +886 5 5342601x4625; fax: +886 5 5312071. E-mail address: chouth@yuntech.edu.tw (T.-H. Chou). the stability of liposomes, an artificial vesicle composed of a lipid bilayer, could be enhanced by the incorporation of cholesterol into the lipid bilayer [13]. A growing number of experimental results demonstrated that cholesterol and its relevant derivatives have potential applications in biomedical science owing to their excellent properties such as biocompatibility, biodegradability, and low toxicity [4,14–23]. Therefore, it would be expected that an amphiphile formed by attachment of a cholesterol moiety to a polar head group exhibits sound biocompatibility. The steroid backbone of cholesterol is a suitable hydrophobic domain for the self-assembly [23–27]. Various amphiphilic choles- terol derivatives with the unique molecular characteristics have been developed and extensively studied [23,27–34]. The feasibil- ity of amphiphilic self-aggregated nanoparticles as hydrophobic drug carriers has been demonstrated [28]. Yang et al. [29] synthe- sized a novel water-soluble amphiphilic sodium alginate derivative on which was grafted three types of cholesteryl group per 100 hexuronic acid residues. It can self-assemble into stable and compact nano-aggregates under the influence of the intra- and intermolecular hydrophobic interactions between cholesteryl moi- eties in NaCl solution. Wang et al. [31] synthesized a series of cholesterol-modified O-carboxymethyl chitosan conjugates, which formed the monodispersed self-aggregated nanoparticles upon sonication in water. Dimeric cholesterol derivatives (DCDs) have recent emerged as one of the most promising platforms for drug delivery due to their rigid structure, strong hydrophobic force 0927-7765/$ – see front matter. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.12.044