Abreu et al. Nanoscale Research Letters 2011, 6:482 http://www.nanoscalereslett.com/content/6/1/482 N A N O E X P R E S S Open Access Nanoliposomes for encapsulation and delivery of the potential antitumoral methyl 6-methoxy-3-(4- methoxyphenyl)-1H-indole-2-carboxylate Ana S Abreu1,2*, Elisabete MS Castanheira1, Maria-João RP Queiroz2, Paula MT Ferreira2, Luís A Vale-Silva3 and Eugénia Pinto3 Abstract A potential antitumoral fluorescent indole derivative, methyl 6-methoxy-3-(4-methoxyphenyl)-1H-indole-2- carboxylate, was evaluated for the in vitro cell growth inhibition on three human tumor cell lines, MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), and NCI-H460 (non-small cell lung cancer), after a continuous exposure of 48 h, exhibiting very low GI50 values for all the cell lines tested (0.25 to 0.33 μM). This compound was encapsulated in different nanosized liposome formulations, containing egg lecithin (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG), DSPC, cholesterol, dihexadecyl phosphate, and DSPE-PEG. Dynamic light scattering measurements showed that nanoliposomes with the encapsulated compound are generally monodisperse and with hydrodynamic diameters lower than 120 nm, good stability and zeta potential values lower than -18 mV. Dialysis experiments allowed to monitor compound diffusion through the lipid membrane, from DPPC/DPPG donor liposomes to NBD-labelled lipid/DPPC/DPPG acceptor liposomes. Introduction Anticancer drugs are crucial agents in the global approach to fight cancer. Drug-loaded nanoparticles provide a per- fect solution to afford higher therapeutic efficacy and/or reducing toxicity and the possibility of targeting cancer tis- sues. Nanoliposomes are one of the best drug delivery sys- tems for low molecular weight drugs, imaging agents, peptides, proteins, and nucleic acids. Nanoliposomes are able to enhance the performance of bioactive agents by improving their bioavailability, in vitro and in vivo stability, as well as preventing their unwanted interactions with other molecules [1-3]. It is believed that the efficient anti- tumor activity can be attributed to the selective delivery and the preferential accumulation of the liposome nano- carrier in the tumor tissue via the enhanced permeability and retention effect [4-6]. Nanoliposomes may contain, in addition to phospholi- pids, other molecules such as cholesterol (Ch) which is an important component of most natural membranes. * Correspondence: anabreu@quimica.uminho.pt 1Centre of Physics (CFUM), University of Minho, Campus de Gualtar, 4710- 057 Braga, Portugal Full list of author information is available at the end of the article The incorporation of Ch can increase stability by modu- lating the fluidity of the lipid bilayer preventing crystalli- zation of the phospholipid acyl chains and providing steric hindrance to their movement. Further advances in liposome research found that surface modification with polyethylene glycol (PEG), which is inert in the body, generally reduces the clearance of liposome by RES, and therefore allows longer circulatory life of the drug deliv- ery system in the blood [3]. Pegylated liposomal doxoru- bicin has shown great prolonged circulation and substantial efficacy in breast cancer treatment [7]. The net charge of nanoliposomes is also an important factor and generally anionic and neutral liposomes survive longer than cationic liposomes in the blood circulation after intravenous injection [8,9]. In the present study, the antitumoral activity of the fluorescent indole derivative 1, methyl 6-methoxy-3-(4- methoxyphenyl)-1H-indole-2-carboxylate (Figure 1), pre- viously synthesized by us [10], was tested for the in vitro growth of three human tumor cell lines, showing very low GI50 values. Considering its promising utility as an antitumoral drug, compound 1 was encapsulated in dif- ferent nanoliposome formulations and the mean size, size © 2011 Abreu et al; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.