Dusan Losic

Graphene and graphene oxide as new nanocarriers for drug delivery applications

The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. Graphene and graphene oxide have been extensively explored as some of the most promising biomaterials for biomedical applications due to their unique properties: two-dimensional planar structure, large surface area, chemical and mechanical stability, superb conductivity and good biocompatibility. These properties result in promising applications for the design of advanced drug delivery systems and delivery of a broad range of therapeutics. In this review we present an overview of recent advances in this field of research. We briefly describe current methods for the surface modification of graphene-based nanocarriers, their biocompatibility and toxicity, followed by a summary of the most appealing examples demonstrated for the delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts based on controlling mechanisms, including targeting and stimulation with pH, chemical interactions, thermal, photo- and magnetic induction, are discussed. Finally the review is summarized, with a brief conclusion of future prospects and challenges in this field.

The Glass Menagerie: diatoms for novel applications in nanotechnology

Diatoms are unicellular, eukaryotic, photosynthetic algae that are found in aquatic environments. Diatoms have enormous ecological importance on this planet and display a diversity of patterns and structures at the nano- to millimetre scale. Diatom nanotechnology, a new interdisciplinary area, has spawned collaborations in biology, biochemistry, biotechnology, physics, chemistry, material science and engineering. We survey diatom nanotechnology since 2005, emphasizing recent advances in diatom biomineralization, biophotonics, photoluminescence, microfluidics, compustat domestication, multiscale porosity, silica sequestering of proteins, detection of trace gases, controlled drug delivery and computer design. Diatoms might become the first organisms for which the gap in our knowledge of the relationship between genotype and phenotype is closed.

Tailoring the surface functionalities of titania nanotube arrays

Nanotubular titanium oxide (TiO(2)) produced by self-ordering processes using electrochemical anodization have been extensively explored in recent years as a new biomaterial for implants, drug delivery systems, cell growth, biosensors, immunoisolations, bioartificial organs and tissue engineering. Chemical inertness is the main weakness of this material when placed in contact with biological systems and surface modification is a possible solution of this problem. The aim of this study is to develop a flexible and facile method for surface modification of TiO(2) nanotubes to tailor new interfacial properties important in many biomedical applications. TiO(2) nanotubes were prepared by electrochemical anodization of titanium foil using ethylene glycol: NH(4)F electrolyte (2% water and 0.3% NH(4)F). Plasma surface modification using allylamine (AA) as a precursor has been applied to generate a thin and chemically reactive polymer (AAPP) film rich in amine groups on top of the TiO(2) nanotube surface. This initial polymer film was used for further surface functionalization by attachment of desired molecules. Two modification techniques were used to demonstrate the flexibility for building of new functionalities on titania nanotube surface: electrostatic adsorption of poly(sodium styrenesulfonate) (PSS) as an example of layer-by-layer assembly (LbL), and covalent coupling of poly(ethylene glycol) (PEG) as an example of creating a protein-resistant surface. These approaches for tailoring the surface chemistry and wettability of TiO(2) nanotubes offer considerable prospects for advancing their interfacial properties to improve existing and develop new functional biomaterials for diverse biomedical applications.

Self-ordered nanopore and nanotube platforms for drug delivery applications

The application of nanotechnology to medicine termed as ‘nanomedicine’ is recognised as an emerging field with enormous potential for developing new therapeutic concepts. A range of nanoscale materials have been explored in the last few years for drug delivery to address the problems associated with conventional drug therapies such as limited drug solubility, poor biodistribution, lack of selectivity and unfavourable pharmacokinetics. Among them, nanoporous materials with ordered and controlled pore structures, high surface area and pore volume, attracted great attention, particularly for implantable drug delivery systems. This review presents the recent progress in this field focused on electrochemically engineered nanopores/nanotube materials such as nanoporous alumina and nanotubular titania. The basic concept of fabrication of these unique materials using a self-ordering process, description of their structural properties, biocompatibility and recent applications for therapeutic implants is presented.

Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion.

Bacterial infection, extensive inflammation and poor osseointegration have been identified as the major reasons for [early] orthopaedic implant failures based on titanium. Creating implants with drug-eluting properties to locally deliver drugs is an appealing way to address some of these problems. To improve properties of titanium for orthopaedic applications, this study explored the modification of titanium surfaces with titaniananotube (TNT) arrays, and approach that combines drug delivery into bone and potentially improved bone integration. A titania layer with an array of nanotube structures (∼120 nm in diameter and 50 μm in length) was synthesized on titanium surfaces by electrochemical anodization and loaded with the water-insoluble anti-inflammatory drug indomethacin. A simple dip-coating process of polymer modification formed thin biocompatible polymer films over the drug-loaded TNTs to create TNTs with predictable drug release characteristics. Two biodegradable and antibacterial polymers, chitosan and poly(lactic-co-glycolic acid), were tested for their ability to extend the drug release time of TNTs and produce favourable bone cell adhesion properties. Dependent on polymer thickness, a significant improvement in the drug release characteristics was demonstrated, with reduced burst release (from 77% to >20%) and extended overall release from 4 days to more than 30 days. Excellent osteoblast adhesion and cell proliferation on polymer-coated TNTs compared with uncoated TNTs were also observed. These results suggest that polymer-modified implants with a TNT layer are capable of delivering a drug to a bone site over an extended period and with predictable kinetics. In addition, favourable bone cell adhesion suggests that such an implant would have good biocompatibility. The described approach is broadly applicable to a wide range of drugs and implants currently used in orthopaedic practice.

Porous Alumina with Shaped Pore Geometries and Complex Pore Architectures Fabricated by Cyclic Anodization

The fabrication of three-dimensional (3D) architectures withnanoscale dimensions is still an evolving research area ofnanotechnology. Various methodologies including conven-tional and unconventional fabrications, such as photolitho-graphy, scanning beam lithography, molding, embossing, andimprinting, have been developed in the past decade.

Controlled drug release from porous materials by plasma polymer deposition.

In this communication, we present a novel approach for control of drug release from porous materials. The method is based on deposition of a plasma polymer layer with controlled thickness which reduces a pore diameter and, hence, defines the rate of drug release.

Synthesis of self-supporting gold microstructures with three-dimensional morphologies by direct replication of diatom templates.

Diatoms (unicellular algae) form porous silica walls (frustule) with intricate, hierarchically organized three-dimensional (3D) structures with micro- to nanoscale dimensions. This paper presents the fabrication of self-supporting gold microstructures with complex 3D morphologies by using electroless gold deposition onto a diatom silica substrate, followed by the substrate removal by acid dissolution. It was demonstrated that gold diatom replicas with distinct micro- to nanoscale structures can be created by a simple and scalable process based on electroless gold deposition. Excellent catalytic properties (catalytic rate constant k = 23.5 +/- 1 x 10(-2) min(-1)) of prepared gold replica catalysts were confirmed for the reduction process of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) in the presence of NaBH(4) as the reductant. This synthetic approach is general and flexible, and it is envisaged that it can be applied for the preparation of a wide range of different metals (Pt, Pd, Ag, Ni, etc.) offering more efficient catalytic, optical, or magnetic properties.

Functionalized diatom silica microparticles for removal of mercury ions

Abstract Diatom silica microparticles were chemically modified with self-assembled monolayers of 3-mercaptopropyl-trimethoxysilane (MPTMS), 3-aminopropyl-trimethoxysilane (APTES) and n-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (AEAPTMS), and their application for the adsorption of mercury ions (Hg(II)) is demonstrated. Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy analyses revealed that the functional groups (–SH or –NH2) were successfully grafted onto the diatom silica surface. The kinetics and efficiency of Hg(II) adsorption were markedly improved by the chemical functionalization of diatom microparticles. The relationship among the type of functional groups, pH and adsorption efficiency of mercury ions was established. The Hg(II) adsorption reached equilibrium within 60 min with maximum adsorption capacities of 185.2, 131.7 and 169.5 mg g−1 for particles functionalized with MPTMS, APTES and AEAPTMS, respectively. The adsorption behavior followed a pseudo-second-order reaction model and Langmuirian isotherm. These results show that mercapto- or amino-functionalized diatom microparticles are promising natural, cost-effective and environmentally benign adsorbents suitable for the removal of mercury ions from aqueous solutions.

Preparation of porous anodic alumina with periodically perforated pores.

Anodization of aluminum is an excellent nonlithographic alternative to conventional fabrication approaches for low-cost and large-scale synthesis of a variety of nanostructured materials. In this work, the preparation of anodic alumina oxide (AAO) with unique three-dimensional (3D) porous structures that consist of periodically perforated nanopores is reported. The fabrication method combines electrochemical anodization of aluminum and chemical etching. The key feature of this process is cyclic anodization where an oscillatory current signal was applied to create AAO with periodically shaped pore structures. Spatially specific dissolution of the pore walls was directed by modulated pore structures during chemical etching to generate hexagonally ordered arrays of holes with periodic distribution across the pore length.