Toward a new generation of nanoparticles for therapy and diagnosis

Progress in utilizing inorganic nanoparticles for biomedical applications has advanced rapidly due to the extensive amount of work done in the synthesis and modification of the materials.1 These nanosized materials provide a robust framework in which two or more components can be incorporated to give multifunctional capabilities. An example can be seen in gold nanomaterials.2 Gold nanoparticles are bioinert, nontoxic, and readily synthesized and functionalized.3 They also provide a multifunctional platform for both therapeutic and diagnostic purposes. Indeed, through proper functionalization, these particles can be engineered to accumulate at illness cells using targeting ligands providing a powerful tool, for example, for gene therapy.4 The biophysico-chemical properties of the vehicle, such as size, charge, surface hydrophilicity, and the nature and density of the ligands on their surface, can all impact the circulating half-life of the particles as well as their biodistribution. Innovation may be introduced by controlling the surface properties of the monolayer protecting the gold core. Indeed, recently it has been demonstrated that particles coated with a molecularly ordered ligand shell were able to enter cells directly through the membrane without perforating it basing on a novel physical chemistry phenomenon.6 This property is ideal as it provides the particles with minimal if none genotoxicity. Mixed monolayers composed of mixtures of hydrogenated/fluorurated ligands favor the phase segregation and consequently the ordered morphology of the NP surface. 7 In addition, the introduction in the monolayer of perfluorocarbon ligands might enable, for example, the imaging by 19F MRI techniques of the nanoparticles and, consequently, the tracking in vivo of cell fate. In this communication we will discuss the approaches for the realization of such innovative nanoparticles easy to make, because obtained by self-assembly strategies, but with an unprecedented degree of complexity, with respect to nanotechnology platforms for drug delivery applications know to date, as far as their features is concerned

Self-organization of mixtures of fluorocarbon and hydrocarbon amphiphilic thiolates on the surface of gold nanoparticles

Self-assembled monolayers composed of mixture of thiolate molecules, featuring hydrocarbon or perfluorocarbon chains (H- and F-chains) terminating with a short poly(oxoethylene) (PEG) moiety is the most extreme example of surfactants immiscibility on gold nanoparticles (NPs) reported so far. The phase-segregation between H-chains and F-chains and the consequent, peculiar folding of PEG chains are responsible for the increased affinity of a selected radical probe for the fluorinated region, which increases as the size of the fluorinated domains decreases, independently of the shape of such domains. This feature has been revealed by ESR measurements and an in silico innovative multiscale molecular simulations approach in explicit water. Our results reveal an underlying mechanism of a transmission of the organization of the monolayer from the inner region close to the gold surface toward the external hydrophilic PEG region. Moreover, this study definitively proves that a mixed monolayer is a complex system with properties markedly different from those characterizing the parent homoligand monolayers

Self-Organization of Mixtures of Fluorocarbon and Hydrocarbon Amphiphilic Thiolates on the Surface of Gold Nanoparticles

Self-assembled monolayers composed of a mixture of thiolate molecules, featuring hydrocarbon or perfluorocarbon chains (H- and F-chains) terminating with a short poly(oxoethylene) (PEG) moiety, are the most extreme example of surfactant immiscibility on gold nanoparticles reported so far. The phase segregation between H-chains and F-chains and the consequent, peculiar folding of PEG chains are responsible for the increased affinity of a selected radical probe for the fluorinated region, which increases as the size of the fluorinated domains decrease, independently of the shape of such domains. This feature has been revealed by ESR measurements and an in silico innovative multiscale molecular simulations approach in explicit water. Our results reveal an underlying mechanism of a transmission of the organization of the monolayer from the inner region close to the gold surface toward the external hydrophilic PEG region. Moreover, this study definitively proves that a mixed monolayer is a complex system with properties markedly different from those characterizing the parent homoligand monolayers