Current Topics in Medicinal Chemistry - Volume 14, Issue 5, 2014

Self-assembly has fascinated many scientists over the past few decades. Rapid advances and widespread interest in the study of this subject has led to the synthesis of an ever-increasing number of elegant and intricate functional structures with sizes that approach nano- and mesoscopic dimensions. Today, it has grown into a mature field of modern science whose interfaces with many disciplines have provided invaluable opportunities for crossing boundaries for scientists seeking to design novel molecular materials exhibiting unusual properties, and for researchers investigating the structure and function of biomolecules. Consequently, self-assembly transcends the traditional divisional boundaries of science and represents a highly interdisciplinary field including nanotechnology and nanomedicine. Basically, self-assembly focuses on a wide range of discrete molecules or molecular assemblies and uses physical transformations to achieve its goals. In this Review, we present a comprehensive overview of the advances in the field of drug self-assembly and discuss in detail the synthesis, self-assembly behavior, and physical properties as well as applications. We refer the reader to past reviews dealing with colloidal molecules and colloidal self-assembly. In the first part, we will discuss, compare, and link the various bioinformatic procedures: Molecular Dynamics and Quantitative Structure Activity Relationship. The second section deals with the self-assembly behavior in more detail, in which we focus on several experimental techniques, selected according to the depth of knowledge obtained. The last part will review the advances in drug-protein assembly. Nature provides many examples of proteins that form their substrate binding sites by bringing together the component pieces in a process of self-assembly. We will focus in the understanding of physical properties and applications developing thereof.

Recent advances in development of potential magnetic nanoparticles for magnetic fluid hyperthermia are summarized. This review covers relation between various size dependent physical properties and their applications subject to modification in synthesis methods. Brief discussion on different heating mechanism of magnetic nanoparticles is provided. This review covers recent progress of various magnetic nanoparticles including core shell type for in vitro, in vivo and pre-clinical trials. The highlight of this review is to build up a bridge between synthesis, surface modification and in vivo- pre-clinical in magnetic fluid hyperthermia.

The present review focuses on core-shell nanostructures of spherical gold nanoparticles (Au NPs) and biocompatible polymers mainly from the view points of preparation approaches, nanocomposite properties and potential applications for biology. The preparation approaches are assorted into direct-reduction, covalent “graft-to”, “graft-from” approach, surface bonding and physical adsorption. Various biocompatible polymers are involved such as the thermosensitive polymers, pH-responsive polymers, antibiofouling polymers, conductive polymers and several natural polymers. The encapsulating and loading properties, cellular uptake and drug release control, as well as biorecognition, targeting and sensing potential are discussed in connection with biological systems. These polymeric gold nanocomposites will have a great potential in biotechnology and life science but also face enormous challenge in future applications.

Lipid membranes are of great importance for many biological systems and biotechnological applications. One method to gain a profound understanding of the dynamics in lipid membranes and their interaction with other system components is by modeling these systems by computer simulations. Many different approaches have been undertaken in this endeavor that have led to molecular level insights into the underlying mechanisms of several experimental observations and biological processes with an extremely high temporal resolution. As compared to the free-standing lipid bilayers, there are fewer simulation studies addressing the systems of supported lipid membranes. Nevertheless, these have significantly enhanced our understanding of the behavior of lipid layers employed in applications spanning from biosensors to drug delivery and for biological processes such as the breathing cycle of lung surfactants. In this review, we give an account of the state of the art of methods and applications of the simulations of supported lipid bilayers, interfacial membranes at the air/water interface and on solid surfaces.

Silicon substrates were irradiated at normal incidence with a femtosecond Ti:sapphire laser (Quatronix, 90 fs pulse duration, 1 kHz repetition rate, M2 ~ 1.2, maximum energy peak 350 mJ ) operating at a wavelength of 400 nm and focused via a microscope objective (Newport; UV Objective Model, 37x 0.11 N.A.). The laser scanning was assisted by liquids precursors media such as methanol and 1,1,2-trichlorotrifluoroethane. By altering the processing parameters, such as incident laser energy, scanning speed, and different irradiation media, various surface structures were produced on areas with 1 mm2 dimensions. We analyzed the dependence of the surface morphology on laser pulse energy, scanning speed and irradiation media. Well ordered areas are developed without imposing any boundary conditions for the capillary waves that coarsens the ripple pattern. To assess biomaterial-driven cell adhesion response we investigated actin filaments organization and cell morphological changes following growth onto processed silicon substrates. Our study of bone cell progenitor interaction with laser nanoprocessed silicon lines has shown that cells anchor mainly to contact points along the nanostructured surface. Consequently, actin filaments are stretched towards the 15 µm wide parallel lines increasing lateral cell spreading and changing the bipolar shape of mesenchymal stem cells.

We report on the structure of whey protein aggregates formed by a short heating coupled to shear at high temperatures (80-120) and neutral pH in scale-up processing conditions, using gel filtration chromatography, light scattering, small angle neutron scattering, and cryogenic transmission electron microscopy. The results are interpreted in terms of coexistence of residual non-aggregated proteins and aggregates. The characteristics of aggregates such as the size, the aggregation number and the shape evidence two different morphologies. Whereas aggregates formed at 80 °C show a selfsimilar structure down to a length scale of the monomer with a fractal dimension typical for reaction limited cluster aggregation (D∼2.2), aggregates formed at higher temperature show a spherical morphology, with the structure from small angle neutron scattering data best modelled with the form factor of a polydisperse sphere. We compare the structure of these aggregates to that of aggregates formed in quiescent conditions at lab scale. The structure transition is interpreted in terms of a non-trivial interplay between three perturbation factors: interparticle interaction, temperature and shear.

Human fibrinogen adsorption on negatively charged latex particles was investigated using the electrophoretic and the concentration depletion methods. Measurements were conducted at pH 7.4 and in the range of ionic strength of 10-3 - 0.15 M NaCl. Firstly, the bulk physicochemical properties of fibrinogen were characterized. The zeta potential and the uncompensated (electrokinetic) charges of the protein were determined from the electrophoretic measurements. Next, systematic experiments were performed to determine the dependencies of the electrophoretic mobility of latex on the amount of adsorbed protein. Electrophoretic mobility increased significantly upon fibrinogen adsorption that was proven irreversible. The maximum coverage of fibrinogen on latex particles determined via the concentration depletion method varied between 1.9 mg m-2 and 3.2 mg m-2 for 10-3 and 0.15 M NaCl, respectively. The changes in the maximum coverage were interpreted as due to electrostatic repulsion among adsorbed protein molecules. Additionally, the stability of latex covered by fibrinogen was determined. It was proven that cyclic changes of ionic strength from 10-3 to 0.15 M NaCl did not change the electrophoretic mobility. Based on these observations, it was concluded that there were no conformational changes within adsorbed fibrinogen molecules. The experimental data, allowed one to elaborate a robust procedure of preparing latex particles covered by fibrinogen of designed coverage and molecule distribution.

The use of cationic lipids (CLs) as transfecting agents of DNA has received an increasing attention in the last two decades. In order to improve the transfection efficiency with lower cytotoxicity, many CLs have been synthesized to be used as non-viral vectors, not only of DNA but also for other nucleic acids. Cationic lipids together with a helper lipid form mixed liposomes that compact DNA forming lipoplexes, gene vectors able to transport DNA into the cells without provoke an immune response. This review is focused in the progress and recent advances experimented in this area, mainly during last decade. Special attention has been paid: (a) to the biophysical characterization (electrostatics, structure, size and morphology) of the lipoplexes using a wide variety of experimental methods and, (b) to the biological studies (transfection efficiency and cell viability/cytotoxicity) addressed to confirm the viability and the optimum formulations of these DNA vectors to be used in gene therapy. Finally, and in order to take advantage towards a rational design of improved lipid gene vectors, the lipoplex structure-biological activity relationship has been also reviewed.

Nanotechnology is revolutionizing the development of different branches of science. The investigation of nanomaterials in the battle against cancer is not an exception. The main goal of this contribution is to bring an overview about the types of organic and inorganic nanomaterials that are under investigation for its applications in different aspects of cancer therapy: detection, diagnosis, contrast agents, controlled drug delivery, and hyperthermia. This review also includes fundamental aspects such as basic properties and synthesis of nanoparticles, with an emphasis on the use of selfassembed systems such as micelles, microemulsions, nanoemulsions, and liposomes.

In this article we review the flow chemistry methodologies for the controlled synthesis of different kind of nano and microparticles for biomedical applications. Injection mechanism has emerged as new alternative for the synthesis of nanoparticles due to this strategy allows achieving superior levels of control of self-assemblies, leading to higher-ordered structures and rapid chemical reactions. Self-assembly events are strongly dependent on factors such as the local concentration of reagents, the mixing rates, and the shear forces, which can be finely tuned, as an example, in a microfluidic device. Injection methods have also proved to be optimal to elaborate microsystems comprising polymer solutions. Concretely, extrusion based methods can provide controlled fluid transport, rapid chemical reactions, and cost-saving advantages over conventional reactors. We provide an update of synthesis of nano and microparticles such as core/shell, Janus, nanocrystals, liposomes, and biopolymeric microgels through flow chemistry, its potential bioapplications and future challenges in this field are discussed.