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In the last years, the development of nano-formulations for cancer treatment represents one of the major challenges of the scientific research. The prodrug strategy, that combines chemotherapeutic agents with nanocarriers such as halloysite nanotubes (HNTs), is a promising strategy both to improve the biological activity of the drug molecules and to reduce the side effects of drugs. Herein we report the synthesis and characterization of a HNTs prodrug based on 1,2,3-triazole units covalently linked to HNTs external surface, bearing different positively charged moieties, which could present interesting pharmacological activities.

Halloysite nanotubes (HNTs) represent a versatile core structure for the design of functional nanosystems of biomedical interest. However, the development of selective methodologies for the site-controlled functionalization of the nanotubes at specific sites is not an easy task. This study aims to accomplish a procedure for the site-selective/specific, “pin-point”, functionalization of HNTs with polydopamine (HNTs@PDA). This goal was achieved, at pH 6.5, by exploiting the basicity of ZnO nanoparticles anchored on the HNTs external surface (HNTs@ZnO) to induce a punctual polydopamine polymerization and coating. The morphology and the chemical composition of the nanomaterial was demonstrated by several techniques. Turbidimetric analysis showed that PDA coating affected the aqueous stability of HNTs@PDA compared to both HNTs@ZnO and HNTs. Notably, hyperthermia studies revealed that the nanomaterial induced a local thermic rise, up to 50 °C, under near-infrared (NIR) irradiation. Furthermore, secondary functionalization of HNTs@PDA by selective grafting of biotin onto the PDA coating followed by avidin binding was also accomplished.

In the last years, the use of clay minerals for pharmaceutical purposes has increased due to their interesting properties. Hectorite (Ht) is a clay belonging to the smectite group which has attracted attention for applications in biology, tissue engineering and as drug carrier and delivery system. However, the mechanisms involved in Ht cellular uptake and transport into cells, are still unclear. Herein, we used a labeled Ht (Ht/1Cl) to study both the cellular uptake, by confocal laser scanning microscopy, and internalization pathways involved in the cellular uptake, by various endocytosis-inhibiting studies and fluorescence microscopy. These studies highlighted that Ht can penetrate the cellular membrane, localizing mainly in the cytoplasm. The main intracellular transport mechanisms are the ATP-dependent ones and those where filaments and microtubules are involved. Finally, as proof of concept for the potential of Ht as carrier system, we envisaged the covalent grafting of the anticancer molecule methotrexate (MTX), chosen as model, to obtain the Ht-MTX nanomaterial. The covalent linkage was confirmed by several techniques and the morphology of the obtained nanomaterial was imaged by SEM and TEM investigations. The kinetic release of the drug from the Ht-MTX nanomaterial in physiological conditions was studied as well. Furthermore, cytotoxic studies on different cell lines, namely, HL-60, HL-60R, MCF-7, 5637, UMUC3 and RT112 showed that Ht could be a promising material for anticancer therapy.

The development of systems able to deliver genetic material into a target site is a challenge for modern medicine. Single-stranded peptide nucleic acids have attracted attention as promising therapeutic molecules for diagnostic and gene therapy. However, their poor cell membrane permeability represents a drawback for biomedical applications. Halloysite nanotubes (HNTs) are emerging materials in drug delivery applications both for their ability to penetrate cell membranes and for enhancing the solubility of drugs in biological media. Herein, we report the first example of the use of a nanocarrier based on halloysite labelled with fluorescent switchable halochromic oxazine molecules, to deliver a single-stranded peptide nucleic acids tetramer (PNAts) into living cells. The PNAts is covalently attached to halloysite (HNTs-PNA), whereas the fluorescent probe supramolecularly interacts with HNTs. The ability of the nanomaterial to bind complementary single-stranded DNA was assessed by resonance light scattering measurements. Finally, studies of cellular uptake were carried out by confocal laser scanning microscopy on normal and tumoral cell lines. This work highlights the usefulness of the covalent approach to generate HNTs-PNA nanomaterials for the potential targeting of future specific nucleic acids in living cells, which could open the doorway to novel possibilities for theranostic and gene therapy applications.

The design of multifunctional nanomaterials which can help the healing processes of skin, preventing the bacterial infections, is crucial for the development of suitable therapy for the treatment of chronic lesions. The use of clay minerals in wound healing applications is well documented since the prehistoric period and offers several advantages due to their intrinsic properties. Herein, we report the development of ciprofloxacin carrier systems based on hectorite/halloysite (Ht/Hal) hybrid hydrogels for potential wound healing applications. To achieve this objective firstly the ciprofloxacin molecules were loaded onto Hal by a supramolecular and covalent approach. The so obtained fillers were thoroughly investigated by several techniques and at molecular level by means of quantum mechanics calculations along with empirical interatomic potentials. Afterwards the modified Hal were used as filler for Ht hydrogels. The introduction of modified Hal, in hectorite hydrogel, helps the gel formation with an improvement of the rheological properties. The in vitro kinetic release from both the fillers and from the hybrid hydrogels was studied both at skin's pH (5.4) and under neutral conditions (pH 7.4); in addition, the factors controlling the ciprofloxacin release process were determined and discussed. Finally, the in vitro biocompatibility of the Hal fillers was evaluated by means of cytotoxic assays and laser scanning confocal microscopy on normal human dermal fibroblasts., The work was carried out in the frame of the PON “AIM: Attrazione e Mobilità Internazionale” No. 1808223-1 project. Authors are thankful to H.A. Duarte for providing atomic coordinates of halloysite, to the CSIC Computational Center and the University of Granada Computation Center for computation facilities, and the Andalusian project grants RNM-1897 and P18-RT-3786 , and the Spanish MINECO projects , PCIN-2017-098 , FIS2016-77692-C2-2-P and CGL2016-80833-R , for the financial support of this research.

Fluorescence imaging has become an indispensable tool in the biomedical laboratory to elucidate the fundamental dynamic and structural factors regulating cellular processes. The development of fluorescent nanoprobes represents a challenge to detect any cellular process under a microscope. Herein, a fluorescent nanomaterial was synthesized by exploiting the supramolecular interaction between a halochromic switch (1Cl) and halloysite nanotubes (HNTs). The successful synthesis of a HNTs/1Cl nanomaterial was confirmed by thermogravimetric analysis and Fourier transform infrared. The aqueous mobility was investigated by dynamic light scattering and ζ-potential measurements as well. Furthermore, the morphology was imaged by transmission electron microscopy, and the interaction of the clay with 1Cl was also studied by kinetic adsorption measurements. In addition, the spectroscopy properties of the resulting nanomaterial were studied in solution and the solid state by UV-vis and fluorescence measurements. Finally, the ability of our nanomaterial to detect cancer cells was assessed with confocal laser scanning microscopy measurements on normal (hTERT) and/or tumoral cell lines (MCF-7 and HL-60R).

The prodrug approach, as well as the development of specific systems able to deliver a chemotherapeutic agent in the target site, decreasing the side effects often associated with its administration, are still a challenging. In this context, both methotrexate drug molecules (MTX) and biotin ligand moieties, whose receptors are overexpressed on the surface of several cancer cells, were loaded on halloysite nanotubes (HNTs) to develop nanomaterial based on multifunctional and "smart" delivery systems. To highlight the crucial role played by biotin, carrier systems based on HNTs and MTX were also synthetized. In detail, several approaches were envisaged: i) a supramolecular interaction between the clay and the drug; ii) a covalent grafting of the drug onto the HNTs external surface and, iii) a combination of both approaches. The nanomaterials obtained were characterized by thermogravimetric analysis, FT-IR, and UV-vis spectroscopies, DLS and ζ-potential measurements and the morphologies were imaged by HAADF/STEM investigations. Kinetic release experiments at different pH conditions were also performed. Finally, as a proof-of-concept application of our pro-drug delivery systems based on HNTs in cancer therapy, the cytotoxic effects were evaluated on acute myeloid leukemia cell lines, HL60 and its multidrug resistance variant, HL60R. The obtained results showed that both the MTX prodrug system and the biotinylated ones played a crucial role in the biological activity and, they are promising agents for the cancer treatments.

Halloysite nanotubes (HNTs) represent a versatile core structure for the design of functional nanosystems of biomedical interest. However, the development of selective methodologies for the site-controlled functionalization of the nanotubes at specific sites is not an easy task. This study aims to accomplish a procedure for the site-selective/specific, ''pin-point", functionalization of HNTs with polydopamine (HNTs@PDA). This goal was achieved, at pH 6.5, by exploiting the basicity of ZnO nanoparticles anchored on the HNTs external surface (HNTs@ZnO) to induce a punctual polydopamine polymerization and coating. The morphology and the chemical composition of the nanomaterial was demonstrated by several techniques. Turbidimetric analysis showed that PDA coating affected the aqueous stability of HNTs@PDA compared to both HNTs@ZnO and HNTs. Notably, hyperthermia studies revealed that the nanomaterial induced a local thermic rise, up to 50 C, under near-infrared (NIR) irradiation.

Carbon nanomaterials are attractive candidates for drug delivery due to their high surface area, ease of functionalisation and biocompatibility. This work describes the spectroscopic monitoring of the loading capacity of oxidised carbon nanohorns for two cationic porphyrins. Addition of the COOH functionalised carbon nanohorns to both meso-tetra(4-N-methylpyridyl) free base (H2TMPyP4) and platinum (PtTMPyP4) porphyrin in aqueous solution results in hypochromism of the Soret band and quenching of the porphyrin emission. These changes are used to monitor the non-covalent binding interactions with the nanohorn surface and determine the surface loading. The colloidal stability of the nanohorns to biologically relevant solution environments as a function of loading is also reported. Finally, we demonstrate photoactivated cell death upon uptake of a colloidally stable PtTMPyP4 CNH hybrid.

Clay minerals have been used for medical purposes from ancient times. Among them, the halloysite nanotube, an aluminosilicate of the kaolin group, is an emerging nanomaterial which possesses peculiar chemical characteristics. By means of suitable modifications, such as supramolecular functionalization or covalent modifications, it is possible to obtain novel nanomaterials with tunable properties for several applications. In this context the covalent grafting of suitable organic moieties on the external surface or in the halloysite lumen has been exploited to improve the loading and release of several biologically active molecules. The resulting hybrid nanomaterials have been applied as drug carrier and delivery systems, as fillers for hydrogels, in tissue regeneration and in the gene delivery field. Furthermore the loading and release of specific molecules have been also investigated for environmental purposes. This review summarizes the main developments in the halloysite modifications in the last 20 years with a particular attention to the development in the past two years.

LAPONITE® (Lap) clay mineral was successful functionalized by triazole groups in a two steps procedure. First, the Lap edges were modified with 3-azidopropyltrimethoxysilane by traditional heating and microwave irradiation. Microwave irradiation allowed us to obtain high loading onto the Lap edges in lower times compared to those obtained through conventional method. Afterwards, the triazole moieties were obtained by reaction between azido functionalized Lap and propargyl alcohol. The successful functionalization of Lap was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and ζ-potential measurements. Finally, the effects of the surface modification on the gel formation ability of Lap were studied by gelation tests and the morphology of the gel phases was investigated by polarized optical microscopy measurements and diffusion experiments.

Halloysite-cyclodextrin hybrid was employed as carrier for sustained release of clotrimazole for vaginal or buccal treatment of Candidiasis. The nanocarrier was obtained by functionalization of halloysite surface with cyclodextrin moieties by means of microwave irradiation, with the final goal to obtain a scaffold for the covalent linkage of cysteamine hydrochloride. The interaction between clotrimazole and the pristine components, namely cyclodextrin and halloysite, was thoroughly investigated by several techniques such as DSC, TGA, UV–vis spectroscopy and some adsorption studies were, also, carried out. The release of the antifungine molecule was finally investigated in a medium that imitates the physiological conditions.

Clays are used in various cosmetic formulations, such as sunscreens, toothpastes, deodorants, creams, hair cosmetics, makeups, nail polish, facial masks, and shampoos, among others, to improve the organoleptic and physicochemical characteristics, to increase the stability, or to facilitate elaboration. Together with their technological functionalities, clays are cosmetologically active ingredients with cleaning, anti-aging, anti-wrinkling, and sun-care functionalities. Talc, kaolinite, mica, and some smectites are the clay minerals used most frequently in cosmetic products, but several other phyllosilicates as well as modified and synthetic clays are also used. Sometimes, clays are useful in the design of cosmetics just because they are made of rigid, small, and anisometric particles. Kaolinite and mica are made of hard prismatic particles which are lightly abrasive over the skin, teeth, or hair. Electric charges in smectites result in ion-exchange capacities useful in the loading of active cosmetics but also adsorbing and cleaning waste substances. Intermediate net negative charges of smectites result in layer expansion in polar media and specific rheological properties that are very useful in cosmetic formulations. The absence of charged particles in talc and kaolin make them flow easily resulting in lubricant effects. Protection against radiation from the sun by clay particles and decorative effects complete the possibilities of clays in cosmetics. The nomenclature for clays used as ingredients in cosmetics follows historical use and the names of commercial products, rather than following strict compositional principles. In this sense, an effort was made here to correlate the names of the minerals that make up each of the clay-based cosmetic ingredients., The work has been supported by funding from the Spanish group CTS-946 and project P18-RT-3786.

The synthesis of pure fine chemicals for industrial purposes is one of the most attractive challenges of chemical research. The use of catalytic pathways mediated by palladium nanoparticles (PdNPs) for C-C bond formation is a useful way to obtain these kinds of compounds. To achieve this objective, the PdNPs can be efficiently loaded on a functionalized natural nanostructured support such as halloysite nanotubes (HNTs). Hybrid materials based on thiol functionalized halloysite nanotubes and highly cross-linked imidazolium salts were successfully developed and used for the stabilization of PdNPs. The HNT/Pd hybrids were thoroughly characterized from a physico-chemical point of view and tested as a catalyst in the Suzuki and Heck C-C coupling reactions under microwave irradiation to obtain innovative materials for fine chemicals synthesis. Catalytic tests highlighted the fact that the HNT/Pd hybrids show high performance and full recyclability (up to ten cycles) in both reactions. Regarding the Suzuki reaction, under the best experimental conditions, the remarkable values of a turnover number of 194 000 and a turnover frequency of 3 880 000 h-1 were achieved without metal contamination in the final products. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. The synthesis of pure fine chemicals for industrial purposes is one of the most attractive challenges of chemical research. The use of catalytic pathways mediated by palladium nanoparticles (PdNPs) for C–C bond formation is a useful way to obtain these kinds of compounds. To achieve this objective, the PdNPs can be efficiently loaded on a functionalized natural nanostructured support such as halloysite nanotubes (HNTs). Hybrid materials based on thiol functionalized halloysite nanotubes and highly crosslinked imidazolium salts were successfully developed and used for the stabilization of PdNPs. The HNT/Pd hybrids were thoroughly characterized from a physico-chemical point of view and tested as a catalyst in the Suzuki and Heck C–C coupling reactions under microwave irradiation to obtain innovative materials for fine chemicals synthesis. Catalytic tests highlighted the fact that the HNT/Pd hybrids show high performance and full recyclability (up to ten cycles) in both reactions. Regarding the Suzuki reaction, under the best experimental conditions, the remarkable values of a turnover number of 194 000 and a turnover frequency of 3 880 000 h1 were achieved without metal contamination in the final products.

Clay minerals are considered one of the materials of the 20th century for their peculiar physico-chemical features. Among them, halloysite nanotubes (HNTs) are an emerging nanomaterial with a particular tubular structure that makes them a low cost and valuable alternative to the most common carbon nanotubes. Due to their tubular morphology, HNTs are employed in several fields acting as nanocontainers for different compounds for applications in drug carrier and delivery fields, catalysis, and as filler for polymeric matrices. The modification of HNTs’ surfaces allows to the synthesis of different nanoarchitectures that can improve the mechanical and thermal performance of polymer as well as they can enhance the use for the loading and release of chemicals. In this review, we summarize our recent results on halloysite functionalization, both supramolecular and covalent, and the application aforementioned fields.

Well designed and safe nano drug carrier systems are an important tool in biomedical applications. The combination of two or more drugs has been used in medicine both to enhance the therapeutic effect and to decrease the side effects of drugs. Biocompatible halloysite nanotubes, that possess two different surfaces, are a suitable nanomaterial for a simultaneous carrier and release of two drugs that can exert a synergistic effect against cancer cells. In this study, three curcumin derivatives and doxorubicin were loaded by supramolecular and covalent linkage at the lumen and external surface of the halloysite nanotubes. The obtained multifunctional systems were characterized by several techniques and the kinetic release of the drugs from the lumen was also investigated. Finally, the cytotoxic effects of the multifunctional carriers were evaluated on different cancer cell lines, namely breast cancer cell lines (SUM-149 and MDA-MB-231) and acute myeloid leukemia cell lines (HL60 and HL60R). The obtained results show promising cytotoxicity activity of the hybrids which is correlated to the nanoparticles size and to the release profile of the drug supramolecularly loaded on Hal surfaces.

The synthesis of a new biocompatible bichromophoric system (CURBO) was developed, by connecting the skeleton of the naturally occurring curcumin to a BODIPY derivative. The system exhibited an intense fluorescence band with maximum at about 510 nm in organic solvent, while its emission spectra in aqueous solution were more complicated and slightly red-shifted, due to the effect of aggregation for the poor solubility of the dyad. To overcome these problems, the bichomophoric system has been loaded into the halloysite nanotubes (HNT). The HNT/CURBO nanocomposite, suspended in aqueous solution, showed an intensity of emission in the red region of the spectrum higher than the one exhibited by the pristine CURBO. The biocompatibility and photophysical behavior of HNT/CURBO nanocomposite were studied using ASC52Telo, h-TERT immortalized adipose-derived mesenchymal stem cells. To investigate the localization of the CURBO alone and in HNT/CURBO, fluorescence epimicroscopy was performed. The HNT/CURBO nanocomposite showed a high propensity to cross cell membranes, resulting in a massive cell uptake around the cell nucleus. Moreover, it lighted up ASC52Telo cells both with intense green and red fluorescence while excited in the blue portion of the electromagnetic spectrum, a phenomenon that could not be observed for the free CURBO. Dual-channel emissions dyes and, in particular, materials, such as the HNT/CURBO nanocomposite, emitting in the red portion of the spectrum have become, in recent decades, particularly fascinating since they can minimize the autofluorescence detection of the cell medium and allow interesting microscopy applications.

Water is essential for humans, animals, and plants; pollutants, usually derived from anthropogenic activities, can have a serious effect on its quality. Heavy metals are significant pollutants and are often highly toxic to living organisms, even at very low concentrations. Among the numerous removal techniques proposed, adsorption onto suitable adsorbent materials is considered to be one of the most promising. The objective of the current study was to determine the effectiveness of halloysite nanotubes (HNT) functionalized with organic amino or thiol groups as adsorbent materials to decontaminate polluted waters, using the removal of Hg2+ ions, one of the most dangerous heavy metals, as the test case. The effects of pH, ionic strength (I), and temperature of the metal ion solution on the adsorption ability and affinity of both materials were evaluated. To this end, adsorption experiments were carried out with no ionic medium and in NaNO3 and NaCl at I = 0.1 mol L−1, in the pH range 3–5 and in the temperature range 283.15–313.15 K. Kinetic and thermodynamic aspects of adsorption were considered by measuring the metal ion concentrations in aqueous solution. Various equations were used to fit experimental data, and the results obtained were explained on the basis of both the adsorbent’s characterization and the Hg2+ speciation under the given experimental conditions. Thiol and amino groups enhanced the adsorption capability of halloysite for Hg2+ ions in the pH range 3–5. The pH, the ionic medium, and the ionic strength of aqueous solution all play an important role in the adsorption process. A physical adsorption mechanism enhanced by ion exchange is proposed for both functionalized materials.

Giuseppa Biddeci,1,2 Gaetano Spinelli,1 Marina Massaro,2 Serena Riela,2 Paola Bonaccorsi,3 Anna Barattucci,3 Francesco Di Blasi1 1Institute for Innovation and Biomedical Research (IRIB), CNR, Palermo, 90146, Italy; 2Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Sect. Chemistry, University of Palermo, Palermo, 90128, Italy; 3Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, 98158, ItalyCorrespondence: Francesco Di BlasiInstitute for Innovation and Biomedical Research (IRIB), CNR, Via Ugo La Malfa 153, Palermo, 90146, ItalyTel +39 0916809514Email francesco.diblasi@irib.cnr.itPurpose: Halloysite nanotubes (HNTs) are a natural aluminosilicate clay with a chemical formula of Al2Si2O5(OH)4×nH2O and a hollow tubular structure. Due to their peculiar structure, HNTs can play an important role as a drug carrier system. Currently, the mechanism by which HNTs are internalized into living cells, and what is the transport pathway, is still unclear. Therefore, this study aimed at establishing the in vitro mechanism by which halloysite nanotubes could be internalized, using phagocytic and non-phagocytic cell lines as models.Methods: The HNT/CURBO hybrid system, where a fluorescent probe (CURBO) is confined in the HNT lumen, has been used as a model to study the transport pathway mechanisms of HNTs. The cytocompatibility of HNT/CURBO on cell lines model was investigated by MTS assay. In order to identify the internalization pathway involved in the cellular uptake, we performed various endocytosis-inhibiting studies, and we used fluorescence microscopy to verify the nanomaterial internalization by cells. We evaluated the haemolytic effect of HNT/CURBO placed in contact with human red blood cells (HRBCs), by reading the absorbance value of the supernatant at 570 nm.Results: The HNT/CURBO is highly biocompatible and does not have an appreciable haemolytic effect. The results of the inhibition tests have shown that the internalization process of nanotubes occurs in an energy-dependent manner in both the investigated cell lines, although they have different characteristics. In particular, in non-phagocytic cells, clathrin-dependent and independent endocytosis are involved. In phagocytic cells, in addition to phagocytosis and clathrin-dependent endocytosis, microtubules also participate in the halloysite cellular trafficking. Upon internalization by cells, HNT/CURBO is localized in the cytoplasmic area, particularly in the perinuclear region.Conclusion: Understanding the cellular transport pathways of HNTs can help in the rational design of novel drug delivery systems and can be of great value for their applications in biotechnology.Keywords: halloysite nanotubes, endocytic pathway, cellular internalization, biocompatibility, hemocompatibility

Uncontrolled cell proliferation is a hallmark of cancer as a result of rapid and deregulated progression through the cell cycle. The inhibition of cyclin-dependent kinases (CDKs) activities is a promising therapeutic strategy to block cell cycle of tumor cells. In this work we reported a new example of nanocomposites based on halloysite nanotubes (HNTs)/pyrazolo[3,4-d]pyrimidine derivatives (Si306 and Si113) as anticancer agents and CDK inhibitors. HNTs/Si306 and HNTs/Si113 nanocomposites were synthesized and characterized. The release kinetics were also investigated. Antitumoral activity was evaluated on three cancer cell lines (HeLa, MDA-MB-231 and HCT116) and the effects on cell cycle arrest in HCT116 cells were evaluated. Finally, molecular dynamics simulations were performed of the complexes between Si113 or Si306 and the active site of both CDK 1 and 2., The work was financially supported by the University of Palermo. The work was carried out in the frame of the PON “AIM: Attrazione e Mobilità Internazionale” No. 1808223 project. SS and GG wish to acknowledge the AIRC project 2019 code 23725. The authors would thank Dr. Susanna Guernelli (University of Bologna) for TEM and SEM measurements.

Halloysite nanotubes (HNTs), clay minerals belonging to the kaolin groups, are emerging nanomaterials which have attracted the attention of the scientific community due to their interesting features, such as low-cost, availability and biocompatibility. In addition, their large surface area and tubular structure have led to HNTs’ application in different industrial purposes. This review reports a comprehensive overview of the historical background of HNT utilization in the last 20 years. In particular it will focus on the functionalization of the surfaces, both supramolecular and covalent, following applications in several fields, including biomedicine, environmental science and catalysis.

A straightforward and economic procedure has been developed for the synthesis of a new polydopamine-like silica-based material that has been obtained by oxidation of catechol with KIO4 followed by reaction with 3-aminopropyltrimethoxysilane. All techniques adopted for characterization showed that the obtained material is rich in different functional groups and the morphological analyses revealed dimensions in the nanometric range. The hybrid material has been characterized by several techniques showing its polydopamine-like nature, and preliminary observations for dye adsorption have been reported., University of Palermo PRIN2017- 2017YJMPZN

A new design for halloysite nanotube materials was obtained by grafting chemically modified cyclodextrin units onto the nanotube surface. In particular, grafted cyclodextrins were decorated with thiosaccharide pendants, in order to mimic the well-known binding of sugars to proteins and the glyco-cluster effect occurring during cellular recognition events. The obtained materials were characterized by using a combination of varied techniques (FT-IR spectroscopy, thermogravimetric analysis, scanning electron microscopy, dynamic light scattering, turbidimetry), and their potential drug-delivery abilities were tested by studying their interactions with the common naturally occurring anticancer agent curcumin. A suitable model describing the interaction between our materials and curcumin is proposed.

In this study, environmental friendly halloysite nanotubes and their amino derivatives were used as adsorbent materials for lead(II) ions. The adsorption ability of both nanomaterials towards Pb2+ ions has been studied in NaClaq, at I = 0.1 mol L−1, in the pH range 3–6. Moreover, the effect of ionic strength on the adsorption process was evaluated at the pH of maximum efficiency of the adsorbent materials. Kinetic and equilibrium experiments were carried out by using the Differential Pulse Anodic Stripping Voltammetry (DP-ASV) technique to check the metal ion concentration in solution after contact with the two adsorbents. Different isotherm and kinetic equations were used to fit the experimental data. The speciation of metal ion and the characterization of the adsorbents with different techniques were considered in order to establish the suitable experimental conditions for the metal ion removal. The collected data showed that the functionalization of halloysite enhances the adsorption ability of the clay mineral and it makes the nanoclay a good candidate for metal removal from aqueous solutions.

The use of clay minerals as catalyst is renowned since ancient times. Among the different clays used for catalytic purposes, halloysite nanotubes (HNTs) represent valuable resources for industrial applications. This special tubular clay possesses high stability and biocompatibility, resistance against organic solvents, and most importantly be available in large amounts at a low cost. Therefore, HNTs can be efficiently used as catalysts themselves or supports for metal nanoparticles in several catalytic processes. This review reports a comprehensive overview of the relevant advances in the use of halloysite in catalysis, focusing the attention on the last five years.

A versatile catalyst based on halloysite and zinc oxide (HNT@ZnO) was prepared, for the first time, starting from ZnO commercial bulk form as Zn precursor source, in a one-pot procedure. This strategy gives the possibility to obtain small ZnO nanoparticles loaded on the HNT surface without the use of inorganic salts which envisage the removal of undesired anions and therefore a calcination process at high temperature. It was found that the presence of halloysite improved the UV–vis spectral absorption ability of ZnO. The hybrid was successful used as photocatalyst for the methylorange and rhodamine B degradation. In addition, after eight consecutive cycles for the methylorange photodegradation, the hybrid did not exhibit significant reduction in its photocatalytic performances confirming its stability. Based on trapping experiments and calculated energy bands we also proposed a photocatalytic mechanism. Furthermore, to evaluate the versatility of the synthetized HNT@ZnO hybrid, we used it as catalyst for biodiesel production from soybean oil, too. Also, in this case, the hybrid showed good catalytic performance and recyclability.

Hypothesis The use of non-viral vectors for gene therapy is hindered by their lower transfection efficiency and their lacking of self-track ability. Experiments This study aims to investigate the biological properties of halloysite nanotubes-carbon dots hybrid and its potential use as non-viral vector for oral gene therapy. The morphology and the chemical composition of the halloysite hybrid were investigated by means of high angle annular dark field scanning TEM and electron energy loss spectroscopy techniques, respectively. The cytotoxicity and the antioxidant activity were investigated by standard methods (MTS, DPPH and H2O2, respectively) using human cervical cancer HeLa cells as model. Studies of cellular uptake were carried out by fluorescence microscopy. Finally, we investigated the loading and release ability of the hybrid versus calf thymus DNA by fluorescence microscopy, circular dichroism, dynamic light scattering and ζ-potential measurements. Findings All investigations performed confirmed the existence of strong electrostatic interactions between the DNA and the halloysite hybrid, so it shows promise as a multi-functional cationic non-viral vector that has also possesses intracellular tracking capability and promising in vitro antioxidant potential.

The synthesis of photoluminescent nanomaterials based on halloysite nanotubes is described. The obtained hybrid was characterized by means of TGA, FT-IR, DLS and XPS measurements; in addition its morphology was imaged by TEM and HR-TEM. The HNT hybrid also exhibited photoluminescent properties, both in solution and in the solid state, and white-light emission (0.24, 0.36; CIE coordinates) was observed. This work could be pioneering as a new strategy for manufacturing both LEDs and fluorescent tags based on HNT nanomaterials. © 2018 The Royal Society of Chemistry.

Clay minerals are phyllosilicates of nanoscale dimensions. According to their ability to entrap and release organic moieties, they have found applications in several fields, such as drug carrier and delivery, support for catalyst, environmental remediation and filler for polymeric matrices. The possibility to modify, by covalent linkage, their surfaces gives the possibility to form new nanomaterials with improved properties respect to the pristine clay minerals. In this chapter, the modifications of the siloxane surfaces of the most representative clay minerals, namely montmorillonite, sepiolites, laponite and halloysite were reviewed and discussed.

Hypothesis: Oral insulin administration is not actually effective due to insulin rapid degradation, inactivation and digestion by proteolytic enzymes which results in low bioavailability. Moreover insulin is poorly permeable and lack of lipophilicity. These limits can be overcome by the loading of protein in some nanostructured carrier such as halloysite nanotubes (HNTs). Experiments: Herein we propose an easy strategy to obtain HNT hybrid materials for the delivery of insulin. We report a detailed description on the thermal behavior and stability of insulin loaded and released from the HNTs hybrid by the combination of several techniques. Findings: Release experiments of insulin from the HNTs revealed the efficacy of the nanocarrier. Circular Dichroism data evidenced that the released insulin exhibits its native-like secondary structure confirming the suitability of HNT/insulin as delivery system for at least three months. The loaded nanotubes were filled into chitosan matrix with the aim to prepare bionanocomposite films that can be used for transdermal delivery. This work puts forward an efficient strategy to prepare halloysite based nanocarriers containing insulin that could be employed in several biomedical applications. The detailed description of the prepared HNT/insulin hybrid represents a fundamental point for designing advanced delivery systems. © 2018 Elsevier Inc.

The use of nanotechnology in several fields has created a great interest and its rapid development with application in material science, nanomedicine, medical diagnosis, computer chips, catalysis and so on. The use of nanomaterials represents various advantages, including size, highly active surfaces, unique physico-chemical properties, and in some cases a controlled release of chemicals. In this context phyto-nanotechnology is growing and has promising application in agricultural aspects, such as use of soil remediation, antioxidants, adsorbents, nano-sensor for detection of soil quality, delivery of fertilizers and many others. Plants are very important components of the terrestrial eco-system and essential for the planet life. Studies on the influence of nanomaterial on plant growth indicate that their influence seed germination in different way depending on the nanoparticle used. Among the different nanomaterials, nanoclays and in particular halloysite are, in the last years, attracted a great interest for their intrinsic properties. Usually, clays are natural, no-toxic and abundant in thousands of tons a low price. The use of nanoclay in nanotechnology not only diminishes the risks of ecotoxicity but also, open up enormous scope for employing nanotechology in agriculture.

Halloysite (HNT) is a promising natural nanosized tubular clay mineral that has many important uses in different industrial fields. It is naturally occurring, biocompatible, and available in thousands of tons at low cost. As a consequence of a hollow cavity, HNT is mainly used as nanocontainer for the controlled release of several chemicals. Chemical modification of both surfaces (inner lumen and outer surface) is a strategy to tune the nanotube's properties. Specifically, chemical modification of HNT surfaces generates a nanoarchitecture with targeted affinity through outer surface functionalization and drug transport ability from functionalization of the nanotube lumen. The primary focus of this review is the research of modified halloysite nanotubes and their applications in biological and medical fields.

Halloysite nanotubes (HNTs) are natural nanomaterials that are biocompatible and available in large amounts at low prices. They are emerging nanomaterials with appealing properties for applications like support for metal nanoparticles (NPs). The potential environmental impacts of NPs can be understood in terms of phytotoxicity. Current research has been focusing on HNT applications in cell or animal models, while their use in plants is limited so their ecotoxicological impact is poorly documented. To date there are no studies on the phytotoxic effects of functionalized halloysites (functionalized-HNTs). To develop a quantitative risk assessment model for predicting the potential impact of HNT-supported palladium nanoparticles (HNT-PdNPs) on plant life, an investigation was undertaken to explore their effects on seed germination, seedling development, and mitotic division in root tip cells of 2 lots of Raphanus sativus L. with different vigor. The results showed that exposure to 1500 mg/L of HNTs, functionalized-HNTs, and HNT-PdNPs had no significant influence on germination, seedling development, xylem differentiation, or mitotic index in both lots. Cytogenetic analyses revealed that treatments with functionalized-HNT significantly increased the number of aberrations in low-vigor seeds. These results suggest that low-vigor seeds represent a model for a stress test that would be useful to monitor the effects of NPs. Moreover the present study offers scientific evidence for the use of halloysite for environmental purposes, supporting the biological safety of HNT-PdNPs. Environ Toxicol Chem 2016;35:2503-2510. © 2016 SETAC.

Hybrid materials based on halloysite nanotubes (HNT) and cucurbit[8]uril (CB[8]) were prepared with the aim to obtain efficient nanosponges towards hydrocarbons both in liquid and vapor phases. The loading on both HNT surfaces and the hybrid morphology were evidenced by FTIR spectroscopy, thermogravimetric analysis and scanning electron microscopy. In order to highlight the interactions in the hybrid 13C {1H} CP-MAS NMR experiments were performed. The aqueous colloidal stability of HNT/CB[8] was highlighted through ζ potential and dynamic light scattering measurements. The HNT/CB[8] composite was employed as nanosponge to capture aromatic oils in aqueous phase as evidenced by fluorescence emission spectra of pyrene. These results were correlated with the adsorption capacity of the hybrid toward toluene in vapor phase. This paper provides an efficient way to prepare a biocompatible hybrid material that could be used as a potential multi-pockets nano-container for decontamination of polluted water and/or air.

Hypothesis Polydopamine (PDA) is widely used as hydrophilic coating for several applications. However, most of the methods studied to improve or manipulate PDA properties are multistep and time-consuming, and there is a need for versatile strategies aimed at controlling and modifying the properties of PDA. Experiments PDA-halloysite nanocomposites were produced under different oxidation conditions in alkaline and acidic media and were characterized by UV–visible and attenuated total refraction- Fourier Transform Infrared spectroscopies, thermogravimetric analysis, porosimetry, scanning electron microscopy, X-ray diffraction and contact angle measurements against the reference PDA polymer. Findings Inclusion of the inorganic halloysite nanofiller in the PDA component was found to affect the thermal properties of the nanocomposite as well as its structure, depending on the experimental conditions. The ability of the nanocomposites to adsorb organic dyes as possible membrane coatings for environmental remediation was also investigated by different models, suggesting promising applications as adsorbents for the treatment of wastewaters.

A thermo-responsive polymer such as poly(N-isopropylacrylamide) (PNIPAAM) was covalently grafted on the external surface of halloysite nanotubes (HNTs) by means of microwave irradiation. This nanomaterial was used as a support and stabilizer for palladium nanoparticles. The obtained HNT–PNIPAAM/PdNPs was characterized by means of TGA, SEM, EDS and TEM analyses. The palladium content of the catalyst was estimated to be 0.4 wt%. The stability of the catalytic material at different temperatures (below and above the PNIPAAM lower critical solution temperature) was tested in the Suzuki reaction under microwave irradiation. In addition, TEM analysis after five consecutive runs was performed. The catalyst showed a good catalytic activity toward the Suzuki cross-coupling reaction between phenylboronic acid and several aryl halides in aqueous media under microwave irradiation and low palladium loading (0.016 mol%, 8 mg of Pd). Turnover numbers (TONs) and frequencies (TOFs) up to 6250 and 37 500 h1, respectively, were reached. The catalyst was easily separated from the reaction mixture by centrifugation and reused for five consecutive cycles with a small drop in its catalytic activity.

Mixed cyclodextrin–calixarene nanosponges were used to prepare some composites with the well known polyphenolic bioactive compounds quercetin and silibinin. The composites were characterized by means of different techniques (UV-vis, FT-IR, microcalorimetry, thermogravimetry), in order to assess their loading and thermal stability. The kinetics of release of the bioactive molecules into aqueous solution were studied at two different pH values (1.0, 6.4), which mimic typical physiological conditions. Finally the possible antiproliferative effects in vitro were assayed towards three triple negative breast cancer cell lines (SUM 149, SUM 159 and MDA-MB-23). Our results point out the role assumed by the triazole linkers, present in the nanosponge network, in affecting both the adsorption abilities of the materials towards the bioactive molecules, and the antiproliferative activity of the composites. This work puts forward an efficient strategy to prepare nanosponge based nanocarriers with three different cavities that could encapsulate two or more drug molecules with different physico-chemical properties.

Environmental friendly halloysite-dicationic triazolium salts (second generation) obtained by subsequent click reactions of a diyne derivative in the presence of 2-azidopropyl-modified halloysite nanotubes, were used as supports for palladium catalyst. Thanks to the high triazolium loading (25%) these materials were able to support higher amount of the metal than that on the monocationic derivative (first generation). Such materials were characterized by thermogravimetric analysis, FT-IR spectroscopy and SEM investigations. The new catalytic system was employed in the ligand free Suzuki cross-coupling under microwave irradiation. A set of solvent, time and% loading of palladium was screened. The palladium catalyst displayed good activity allowing the synthesis of several biphenyl in high yields working with only 0.1 mol% of palladium loading at 120 °C in water, for an irradiation time of 10 min. The second generation catalyst, also, showed good recyclability without any loss in activity and negligible palladium leaching that are significant improvements over the first generation triazolium catalyst.

The grafting of poly(N-isopropylacrylamide) (PNIPAAM) onto the halloysite external surface is proposed in order to obtain a novel thermoresponsive drug carrier for curcumin delivery. The new nanomaterial is characterized by means of FT-IR spectroscopy, thermogravimetric analysis, and SEM investigations. A high density of polymer chain was achieved at the nanoparticle surface. The PNIPAAM dehydration phenomenon was observed in water above 32 °C that is nearly coincident with the lower critical solution temperature for the polymer. The colloidal stability as well as the wettability of the obtained nanomaterial may be triggered by temperature stimuli. In vitro tests simulating the gastro-intestinal transit demonstrated that the proposed delivery system allows a targeted release of curcumin, preventing its degradation in an acidic medium. We synthesized a new hybrid nanoparticle that is very promising for several applications due to the copresence of a biocompatible region, to the temperature response, and to the hollow cavity, which can load active species.

Hybrid material based on halloysite covalently linked to a hyper-reticulated cyclodextrin network was investigated as a potential carrier for polyphenolic compounds. The absorption ability of the hybrid system was studied in different pH conditions as well as the kinetic release of curcumin, chosen as a drug model. A preliminary study was performed to assess the antioxidant capacity of the obtained carrier. The obtained results highlighted that the curcumin molecule can have sustained release from the carrier over the time, retaining its antioxidant properties due to the combination of two different host systems that give rise to an hyper-reticulated structure, allowing an increase in the drug loading and stabilization. Therefore, this work puts forward an efficient strategy to prepare organic-inorganic hybrids with three different cavities that could encapsulate two or more drug molecules with different physico-chemical properties.

The goal of modern research is to use environmentally preferable materials. In this context, clay minerals are emerging candidates for their bio- and ecocompatibility, low cost and natural availability. Clay minerals present different morphologies according to their layer arrangements. The use of clay minerals, especially in biomedical applications is known from ancient times and they are regaining attention in recent years. The most representative clay minerals are kaolinit, montmorillonite, sepiolites and halloysite. This review summarizes some clay minerals and their derivatives for application as nanocontainer for biologically active species.