The Horizons of Medical Mineralogy: Structure-Bioactivity Relationship and Biomedical Applications of Halloysite Nanoclay.

Medical mineralogy explores the interactions between natural minerals and living organisms such as cells, tissues, and organs and develops therapeutic and diagnostic applications in drug delivery, medical devices, and healthcare materials. Many minerals (especially clays) have been recognized for pharmacological activities and therapeutic potential. Halloysite clay (Chinese medicine name: Chishizhi), manifested as one-dimensional aluminum silicate nanotubes (halloysite nanotubes, HNTs), has gained applications in hemostasis, wound repair, gastrointestinal diseases, tissue engineering, detection and sensing, cosmetics, and daily chemicals formulations.

Ru/CdS Quantum Dots Templated on Clay Nanotubes as Visible-Light-Active Photocatalysts: Optimization of S/Cd Ratio and Ru Content.

A nanoarchitectural approach based on in situ formation of quantum dots (QDs) within/outside clay nanotubes was developed. Efficient and stable photocatalysts active under visible light were achieved with ruthenium-doped cadmium sulfide QDs templated on the surface of azine-modified halloysite nanotubes. The catalytic activity was tested in the hydrogen evolution reaction in aqueous electrolyte solutions under visible light.

Targeted and Stimulus-Responsive Delivery of Surfactant to the Oil-Water Interface for Applications in Oil Spill Remediation.

The use of chemical dispersants is a well-established approach to oil spill remediation where surfactants in an appropriate solvent are contacted with the oil to reduce the oil-water interfacial tension and create small oil droplets capable of being sustained in the water column. Dispersant formulations typically include organic solvents, and to minimize environmental impacts of dispersant use and avoid surfactant wastage it is beneficial to use water-based systems and target the oil-water interface. The approach here involves the tubular clay minerals known as halloysite nanotubes (HNTs) that serve as nanosized reservoir for surfactants.

Sonication-assisted Layer-by-Layer self-assembly nanoparticles for resveratrol delivery.

This paper advances the development of a novel drug nanodelivery solution to the oral administration of resveratrol (RSV), a low soluble drug whose recognized therapeutic applications are circumscribed when administered in the free compound form. Layer-by-Layer (LbL) self-assembly is an emergent nanotechnology proposed to address this concern with means to afford control over key formulation parameters, which are able to ultimately promote an improved pharmacokinetics. LbL self-assembly consists in the sequential adsorption of oppositely charged polyelectrolytes upon a low soluble drug nanoparticle (NP) template, giving rise to onion-like multilayered nanoarchitectures.

Investigation of Amphiphilic Polypeptoid-Functionalized Halloysite Nanotubes as Emulsion Stabilizer for Oil Spill Remediation.

Halloysite nanotubes (HNTs), naturally occurring and environmental benign clay nanoparticles, have been successfully functionalized with amphiphilic polypeptoid polymers by surface-initiated polymerization methods and investigated as emulsion stabilizers toward oil spill remediation. The hydrophilicity and lipophilicity balance (HLB) of the grafted polypeptoids was shown to affect the wettability of functionalized HNTs and their performance as stabilizers for oil-in-water emulsions. The functionalized HNTs having relatively high hydrophobic content (HLB = 12.

Fluorescence and Cytotoxicity of Cadmium Sulfide Quantum Dots Stabilized on Clay Nanotubes.

Quantum dots (QD) are widely used for cellular labeling due to enhanced brightness, resistance to photobleaching, and multicolor light emissions. CdS and CdZn₁S nanoparticles with sizes of 6⁻8 nm were synthesized via a ligand assisted technique inside and outside of 50 nm diameter halloysite clay nanotubes (QD were immobilized on the tube's surface). The halloysite⁻QD composites were tested by labeling human skin fibroblasts and prostate cancer cells.

Molecular dynamics of the halloysite nanotubes.

We report large-scale and long-time molecular dynamics simulations demonstrating the transformation of a single kaolin alumosilicate sheet to a halloysite nanotube. The models we consider contain up to 5 × 10 atoms, which is two orders of magnitude larger than that used in previous theoretical works. It was found that the temperature plays a crucial role in the formation of the rolled geometry of the halloysite.

Bacterial proliferation on clay nanotube Pickering emulsions for oil spill bioremediation.

Halloysites (tubular aluminosilicate) are introduced as inexpensive natural nanoparticles that form and stabilize oil-water emulsions. Pickering emulsification can proceed with energies low enough to be afforded by ocean turbulence and the stability of droplets extends over more than a week. The oil/water interface is shown to be roughened and bacteria, which are added for oil degradation, are better attached to such oil droplets than to droplets without halloysites.

Nanoparticles Formed onto/into Halloysite Clay Tubules: Architectural Synthesis and Applications.

Nanoparticles, being objects with high surface area are prone to agglomeration. Immobilization onto solid supports is a promising method to increase their stability and it allows for scalable industrial applications, such as metal nanoparticles adsorbed to mesoporous ceramic carriers. Tubular nanoclay - halloysite - can be an efficient solid support, enabling the fast and practical architectural (inside / outside) synthesis of stable metal nanoparticles.

Rapid and Controlled In Situ Growth of Noble Metal Nanostructures within Halloysite Clay Nanotubes.

A rapid (≤2 min) and high-yield low-temperature synthesis has been developed for the in situ growth of gold nanoparticles (NPs) with controlled sizes in the interior of halloysite nanotubes (HNTs). A combination of HAuCl in ethanol/toluene, oleic acid, and oleylamine surfactants and ascorbic acid reducing agent with mild heating (55 °C) readily lead to the growth of targeted nanostructures. The sizes of Au NPs are tuned mainly by adjusting nucleation and growth rates.

Formation of metal clusters in halloysite clay nanotubes.

We developed ceramic core-shell materials based on abundant halloysite clay nanotubes with enhanced heavy metal ions loading through Schiff base binding. These clay tubes are formed by rolling alumosilicate sheets and have diameter of .50 nm, a lumen of 15 nm and length ~1 μm.

Application of halloysite clay nanotubes as a pharmaceutical excipient.

Halloysite nanotubes, a biocompatible nanomaterial of 50-60nm diameter and ca. 15nm lumen, can be used for loading, storage and sustained release of drugs either in its pristine form or with additional polymer complexation for extended release time. This study reports the development composite tablets based on 50wt.

Nanoshell Assembly for Magnet-Responsive Oil-Degrading Bacteria.

The modified polyelectrolyte-magnetite nanocoating was applied to functionalize the cell walls of oil decomposing bacteria Alcanivorax borkumensis. Cationic coacervate of poly(allylamine) and 20 nm iron oxide nanoparticles allowed for a rapid single-step encapsulation process exploiting electrostatic interaction with bacteria surfaces. The bacteria were covered with rough 70-100-nm-thick shells of magnetite loosely bound to the surface through polycations.

The application of halloysite tubule nanoclay in drug delivery.

Introduction: Natural and biocompatible clay nanotubes are among the best inorganic materials for drug nanoformulations. These halloysite tubes with SiO2 on the outermost surface have diameter of ca. 50 nm, length around 1 micrometer and may be loaded with drugs at 10-30 wt.

Clay nanotube-biopolymer composite scaffolds for tissue engineering.

Porous biopolymer hydrogels doped at 3-6 wt% with 50 nm diameter/0.8 μm long natural clay nanotubes were produced without any cross-linkers using the freeze-drying method. The enhancement of mechanical strength (doubled pick load), higher water uptake and thermal properties in chitosan-gelatine-agarose hydrogels doped with halloysite was demonstrated.

Enzyme-activated intracellular drug delivery with tubule clay nanoformulation.

Fabrication of stimuli-triggered drug delivery vehicle s is an important milestone in treating cancer. Here we demonstrate the selective anticancer drug delivery into human cells with biocompatible 50-nm diameter halloysite nanotube carriers. Physically-adsorbed dextrin end stoppers secure the intercellular release of brilliant green.

Spherical and tubule nanocarriers for sustained drug release.

We discuss new trends in Layer-by-Layer (LbL) encapsulation of spherical and tubular cores of 50-150 nm diameter and loaded with drugs. This core size decrease (from few micrometers to a hundred of nanometers) for LbL encapsulation required development of sonication assistant non-washing technique and shell PEGylation to reach high colloidal stability of drug nanocarriers at 2-3mg/mL concentration in isotonic buffers and serum. For 120-170 nm spherical LbL nanocapsules of low soluble anticancer drugs, polyelectrolyte shell thickness controls drug dissolution.

Proteomic profiling of halloysite clay nanotube exposure in intestinal cell co-culture.

Halloysite is aluminosilicate clay with a hollow tubular structure with nanoscale internal and external diameters. Assessment of halloysite biocompatibility has gained importance in view of its potential application in oral drug delivery. To investigate the effect of halloysite nanotubes on an in vitro model of the large intestine, Caco-2/HT29-MTX cells in monolayer co-culture were exposed to nanotubes for toxicity tests and proteomic analysis.

Biomimetic cell-mediated three-dimensional assembly of halloysite nanotubes.

Biomimetic architectural assembly of clay nanotube shells on yeast cells was demonstrated producing viable artificial hybrid inorganic-cellular structures (armoured cells). These modified cells were preserved for one generation resulting in the intact second generation of cells with delayed germination.

Architectural layer-by-layer assembly of drug nanocapsules with PEGylated polyelectrolytes.

150-200 nm diameter capsules containing 60-70 wt % of poorly soluble drugs, paclitaxel and camptothecin, were produced by layer-by-layer (LbL) assembly on drug nanocores in a solution containing uncharged stabilizers. Optimization of capsule shell architecture and thickness allowed for concentrated (3-5 mg/mL) colloids that are stable in isotonic salt buffers. Nanoparticle aggregation during the washless LbL-assembly was prevented by using low molecular weight block-copolymers of poly(amino acids) (poly-L-lysine and poly-L-glutamic acid) with polyethylene glycol (PEG) in combination with heparin and bovine serum albumin at every bilayer building step.

Halloysite clay nanotubes for resveratrol delivery to cancer cells.

Halloysite is natural aluminosilicate clay with hollow tubular structure which allows loading with low soluble drugs using their saturated solutions in organic solvents. Resveratrol, a polyphenol known for having antioxidant and antineoplastic properties, is loaded inside these clay nanotubes lumens. Release time of 48 h is demonstrated.

"Face-lifting" and "make-up" for microorganisms: layer-by-layer polyelectrolyte nanocoating.

Layer-by-layer encapsulation of living biological cells and other microorganisms via sequential adsorption of oppositely charged functional nanoscale components is a promising instrument for engineering cells with enhanced properties and artificial microorganisms. Such nanoarchitectural shells assembled in mild aqueous conditions provide cells with additional abilities, widening their functionality and applications in artificial spore formation, whole-cell biosensors, and fabrication of three-dimensional multicellular clusters.

Selective modification of halloysite lumen with octadecylphosphonic acid: new inorganic tubular micelle.

Selective fatty acid hydrophobization of the inner surface of tubule halloysite clay is demonstrated. Aqueous phosphonic acid was found to bind to alumina sites at the tube lumen and did not bind the tube's outer siloxane surface. The bonding was characterized with solid-state nuclear magnetic resonance ((29)Si, (13)C, (31)P NMR), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy.

Lapatinib/Paclitaxel polyelectrolyte nanocapsules for overcoming multidrug resistance in ovarian cancer.

The sonication-assisted layer-by-layer (SLBL) technology was developed to combine necessary factors for an efficient drug-delivery system: (i) control of nanocolloid size within 100 - 300 nm, (ii) high drug content (70% wt), (iii) shell biocompatibility and biodegradability, (iv) sustained controlled release, and (v) multidrug-loaded system. Stable nanocolloids of Paclitaxel (PTX) and lapatinib were prepared by the SLBL method. In a multidrug-resistant (MDR) ovarian cancer cell line, OVCAR-3, lapatinib/PTX nanocolloids mediated an enhanced cell growth inhibition in comparison with the PTX-only treatment.