This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and conjugation with biological and biocompatible ligands, plasmon-based labeling and imaging, optical and electrochemical sensing, diagnostics, therapy (drug vectorization and DNA/gene delivery) for various diseases, in particular cancer (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the essential in vitro and in vivo toxicity. It will interest the medicine, chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities (211 references).

Figure 19. Current-voltage-luminance curves for two LEDs made of dendrimers. Reprinted with permission from ref 397 (Choi's group).

The binding of peripheral proteins to membranes results in different biological effects. The large diversity of membrane lipids is thought to modulate the activity of these proteins. However, information on the selective binding of peripheral proteins to membrane lipids is still largely lacking. Lipid monolayers at the air/water interface are useful model membrane systems for studying the parameters responsible for peripheral protein membrane binding. We have thus measured the maximum insertion pressure (MIP) of two proteins from the photoreceptors, Retinitis pigmentosa 2 (RP2) and recoverin, to estimate their binding to lipid monolayers. Photoreceptor membranes have the unique characteristic that more than 60% of their fatty acids are polyunsaturated, making them the most unsaturated natural membranes known to date. These membranes are also thought to contain significant amounts of saturated phospholipids. MIPs of RP2 and recoverin have thus been measured in the presence of saturated and polyunsaturated phospholipids. MIPs higher than the estimated lateral pressure of biomembranes have been obtained only with a saturated phospholipid for RP2 and with a polyunsaturated phospholipid for recoverin. A new approach was then devised to analyze these data properly. In particular, a parameter called the synergy factor allowed us to highlight the specificity of RP2 for saturated phospholipids and recoverin for polyunsaturated phospholipids as well as to demonstrate clearly the preference of RP2 for saturated phospholipids that are known to be located in microdomains.

Water-soluble arene-cored "clicked" and non-"clicked" dendrimers terminated by 27, 81, and 243 triethyleneglycol (TEG) tethers (respectively generations G0, G1, and G2) have been synthesized and shown to form dendrimer-encapsulated gold nanoparticles (DEAuNPs) and dendrimer-stabilized gold nanoparticles (DSAuNPs). The dendrimers have been characterized by IR, (1)H NMR, (13)C NMR, size-exclusion chromatography, elemental analysis, MALDI-TOF mass spectroscopy, DOSY NMR, and dynamic light scattering. The AuNPs have been generated and stabilized by these PEGylated dendrimers using a variety of reduction modes, including NaBH(4) in methanol, various single-electron metallocene-type reductants, and even in the absence of additional reductants. The active role of the "clicked" triazole rings, dendrimer generation, stoichiometry of Au precursor, and nature of the reductant and of the solvent are delineated, leading to DSAuNPs with the G0 dendrimer and smaller DEAuNPs with the G1 and G2 dendrimers. Altogether, AuNPs in the size range from 1.8 to 42 nm were formed and characterized by transmission electron microscopy (TEM), high resolution TEM (HRTEM) and UV-vis spectroscopy. Both 1,2,3-triazole and PEGylated Percec-type dendrons are required in the dendrimer structure for the stabilization of AuNPs upon NaBH(4) reduction of HAuCl(4) in methanol. On the other hand, in the absence of other reductant in water, only PEGylated Percec-type dendrons in dendrimers were found to be indispensable, because of their semicavitand shape, for the spontaneous reduction of HAuCl(4) and stabilization of DSAuNPs.

Difficulties previously encountered in the very useful "click" functionalization of gold nanoparticles (AuNPs) resulting in low yields are now overcome by using specific conditions: 1:1 water-THF medium, stoichiometric CuSO(4) and sodium ascorbate, inert atmosphere at 20 degrees C that provide quantitative "click" reactions between azidoalkylthiolate-AuNPs with various hydrophilic (PEG-containing) and hydrophobic (organic and organometallic) alkynes.

Water-soluble benzoate-terminated dendrimers of four generations (from G0 with 9 branches to G3 with 243 branches) were synthesized and fully characterized. They form water-soluble assemblies by ion-pairing interactions with three cations of medicinal interest (acetylcoline, benzyltriethylammonium, and dopamine), which were characterized and investigated by 1H NMR spectroscopy, whereas such interactions do not provoke any significant shift of 1H NMR signals with the monomeric benzoate anion. The calculated association constants confirm that the dendritic carboxylate termini reversibly form ion pairs and aggregates. Diffusion coefficients and hydrodynamic diameters of the dendrimers, as well as changes thereof on interaction with the cations, were evaluated by DOSY experiments. The lack of increase of dendrimer size on addition of the cations and the upfield shifts of the 1H NMR signals of the cation indicate encapsulation within the hydrophobic dendrimer interiors together with probable backfolding of the benzoate termini.

Many research projects are underway to improve the diagnosis and therapy in ophthalmology. Indeed, visual acuity deficits affect 285 million people worldwide and different strategies are being developed to strengthen patient care. One of these strategies is the use of gold nanoparticles (GNP) for their multiple properties and their ability to be used as both diagnosis and therapy tools. This review exhaustively details research developing GNPs for use in ophthalmology. The toxicity of GNPs and their distribution in the eye are described through in vitro and in vivo studies. All publications addressing the pharmacokinetics of GNPs administered in the eye are extensively reviewed. In addition, their use as biosensors or for imaging with optical coherence tomography is illustrated. The future of GNPs for ophthalmic therapy is also discussed. GNPs can be used to deliver genes or drugs through different administration routes. Their antiangiogenic and anti-inflammatory properties are of great interest for different ocular pathologies. Finally, GNPs can be used to improve stereotactic radiosurgery, brachytherapy, and photothermal therapy because of their many properties.

Langmuir monolayers were used to characterize the influence of the physical state of phospholipid monolayers on the binding of protein Retinis Pigmentosa 2 (RP2). The binding parameters of RP2 (maximum insertion pressure (MIP), synergy and ΔΠ(0)) in monolayers were thus analyzed in the presence of phospholipids bearing increasing fatty acyl chain lengths at temperatures where their liquid-expanded (LE), liquid-condensed (LC), or solid-condensed (SC) states can be individually observed. The data show that a larger value of synergy is observed in the LC/SC states than in the LE state, independent of the fatty acyl chain length of phospholipids. Moreover, both the MIP and the ΔΠ(0) increase with the fatty acyl chain length when phospholipids are in the LC/SC state, whereas those binding parameters remain almost unchanged when phospholipids are in the LE state. This effect of the phospholipid physical state on the binding of RP2 was further demonstrated by measurements performed in the presence of a phospholipid monolayer showing a phase transition from the LE to the LC state at room temperature. The data collected are showing that very similar values of MIP but very different values of synergy and ΔΠ(0) are obtained in the LE (below the phase transition) and LC (above the phase transition) states. In addition, the binding parameters of RP2 in the LE (below the phase transition) as well as in the LC (above the phase transition) states were found to be indistinguishable from those where single LC and LE states are respectively observed. The preference of RP2 for binding phospholipids in the LC state was then confirmed by the observation of a large modification of the shape of the LC domains in the phase transition. Therefore, protein binding parameters can be strongly influenced by the physical state of phospholipid monolayers. Moreover, measurements performed with the α/β domain of RP2 strongly suggest that the β helix of RP2 plays a major role in the preferential binding of this protein to phospholipids in the LC state.