Synthesis, Characterization, and Cytotoxicity Evaluation of Novel Water-Soluble Cationic Platinum(II) Organometallic Complexes with Phenanthroline and Imidazolic Ligands.

Platinum-based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water-soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1-C2H4OEt)(phen)] (1, phen=1,10-phenanthroline) precursor, specifically [Pt(NH3)(η1-C2H4OEt)(phen)]Cl (2), [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl (3), and [Pt(1-hexyl-1H-benzo[d]imidazole)(η1-C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki-1), and normal human renal cells (HK-2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki-1) among the tested complexes, compared to healthy cells (HK-2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum-based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties.

Chitosan-Coated Fosetyl-Al Nanocrystals efficacy on Nicotiana tabacum colonized by Xylella fastidiosa.

Xylella fastidiosa (Xf) is a quarantine plant pathogen capable of colonizing the xylem of a wide range of hosts. Currently, there is no cure able to eliminate the pathogen from a diseased plant, whereas several integrated strategies have been implemented for containing the spread of Xf. Nanotechnology represents an innovative strategy based on the possibility of maximizing the potential antibacterial activity by increasing the surface-to-volume ratio of nanoscale formulations. Nanoparticles based on Chitosan and/or Fosetyl-Al have shown different in vitro antibacterial efficacy against Xf subspecies fastidiosa (Xff) and pauca (Xfp). This work demonstrated the uptake of Chitosan-Coated Fosetyl-Al nanocrystals (CH-nanoFos) by roots and their localization in the stems and leaves of olea europaea plants. Additionally, the antibacterial activity of Fosetyl-Al, nano-Fosetyl, nano-chitosan, and Chitosan-Coated Fosetyl-Al nanocrystals (CH-nanoFos) was tested on Nicotiana tabacum cv. SR1 (Petite Havana) inoculated with Xff, Xfp, or Xf subsp. multiplex (Xfm). The bacterial load was evaluated with qPCR, and the results showed that CH-nanoFos was the only treatment able of reducing the colonization of Xff, Xfm, and Xfp in tobacco plants. Additionally, the Area Under Disease Progress Curve (AUDPC), used to assess symptoms development in tobacco plants inoculated with Xff, Xfm, and Xfp and treated with CH-nanoFos, showed a reduction in symptom development. Furthermore, the twitching assay and bacterial growth under microfluidic conditions confirmed the antibacterial activity of CH-nanoFos.

Cellulose Nanocrystal-Based Emulsion of Thyme Essential Oil: Preparation and Characterisation as Sustainable Crop Protection Tool.

Essential oil-based pesticides, which contain antimicrobial and antioxidant molecules, have potential for use in sustainable agriculture. However, these compounds have limitations such as volatility, poor water solubility, and phytotoxicity. Nanoencapsulation, through processes like micro- and nanoemulsions, can enhance the stability and bioactivity of essential oils. In this study, thyme essential oil from supercritical carbon dioxide extraction was selected as a sustainable antimicrobial tool and nanoencapsulated in an oil-in-water emulsion system. The investigated protocol provided high-speed homogenisation in the presence of cellulose nanocrystals as stabilisers and calcium chloride as an ionic crosslinking agent. Thyme essential oil was characterised via GC-MS and UV-vis analysis, indicating rich content in phenols. The cellulose nanocrystal/essential oil ratio and calcium chloride concentration were varied to tune the nanoemulsions' physical-chemical stability, which was investigated via UV-vis, direct observation, dynamic light scattering, and Turbiscan analysis. Transmission electron microscopy confirmed the nanosized droplet formation. The nanoemulsion resulting from the addition of crosslinked nanocrystals was very stable over time at room temperature. It was evaluated for the first time on Pseudomonas savastanoi pv. savastanoi, the causal agent of olive knot disease. In vitro tests showed a synergistic effect of the formulation components, and in vivo tests on olive seedlings demonstrated reduced bacterial colonies without any phytotoxic effect. These findings suggest that crosslinked cellulose nanocrystal emulsions can enhance the stability and bioactivity of thyme essential oil, providing a new tool for crop protection.

HPLC-MS/MS method applied to an untargeted metabolomics approach for the diagnosis of "olive quick decline syndrome".

Olive quick decline syndrome (OQDS) is a disorder associated with bacterial infections caused by Xylella fastidiosa subsp. pauca ST53 in olive trees. Metabolic profile changes occurring in infected olive trees are still poorly investigated, but have the potential to unravel reliable biomarkers to be exploited for early diagnosis of infections. In this study, an untargeted metabolomic method using high-performance liquid chromatography coupled to quadrupole-time-of-flight high-resolution mass spectrometry (HPLC-ESI-Q-TOF-MS) was used to detect differences in samples (leaves) from healthy (Ctrl) and infected (Xf) olive trees. Both unsupervised and supervised data analysis clearly differentiated the groups. Different metabolites have been identified as potential specific biomarkers, and their characterization strongly suggests that metabolism of flavonoids and long-chain fatty acids is perturbed in Xf samples. In particular, a decrease in the defence capabilities of the host after Xf infection is proposed because of a significant dysregulation of some metabolites belonging to flavonoid family. Moreover, oleic acid is confirmed as a putative diffusible signal factor (DSF). This study provides new insights into the host-pathogen interactions and confirms LC-HRMS-based metabolomics as a powerful approach for disease-associated biomarkers discovery in plants.

A Metabolomic Approach Applied to a Liquid Chromatography Coupled to High-Resolution Tandem Mass Spectrometry Method (HPLC-ESI-HRMS/MS): Towards the Comprehensive Evaluation of the Chemical Composition of Cannabis Medicinal Extracts.

INTRODUCTION: Cannabis sativa L. is a powerful medicinal plant and its use has recently increased for the treatment of several pathologies. Nonetheless, side effects, like dizziness and hallucinations, and long-term effects concerning memory and cognition, can occur. Most alarming is the lack of a standardised procedure to extract medicinal cannabis. Indeed, each galenical preparation has an unknown chemical composition in terms of cannabinoids and other active principles that depends on the extraction procedure. OBJECTIVE: This study aims to highlight the main differences in the chemical composition of Bediol® extracts when the extraction is carried out with either ethyl alcohol or olive oil for various times (0, 60, 120 and 180 min for ethyl alcohol, and 0, 60, 90 and 120 min for olive oil). METHODOLOGY: Cannabis medicinal extracts (CMEs) were analysed by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) using an untargeted metabolomics approach. The data sets were processed by unsupervised multivariate analysis. RESULTS: Our results suggested that the main difference lies in the ratio of acid to decarboxylated cannabinoids, which dramatically influences the pharmacological activity of CMEs. Minor cannabinoids, alkaloids, and amino acids contributing to this difference are also discussed. The main cannabinoids were quantified in each extract applying a recently validated LC-MS and LC-UV method. CONCLUSIONS: Notwithstanding the use of a standardised starting plant material, great changes are caused by different extraction procedures. The metabolomics approach is a useful tool for the evaluation of the chemical composition of cannabis extracts. Copyright © 2017 John Wiley & Sons, Ltd.

Thiophene-based fluorescent probes with low cytotoxicity and high photostability for lysosomes in living cells.

BACKGROUND: Selective imaging of lysosomes by fluorescence microscopy using specific fluorescent probes allows the study of biological processes and it is potentially useful also for diagnosis. Lysosomes are involved in numerous physiological processes, such as bone and tissue remodeling, plasma membrane repair, and cholesterol homeostasis, along with cell death and cell signaling. Despite the great number of dyes available today on the market, the search for new fluorescent dyes easily up-taken by cells, biocompatible and bearing bright and long-lasting fluorescence is still a priority. METHODS: Two thiophene-based fluorescent dyes, TC1 and TC2, were synthetized as lysosome-specific probes. RESULTS: The new dyes showed high selectivity for fluorescent staining and imaging of lysosomes and disclosed high photostability, low toxicity and pH insensitivity in the range 2-10. CONCLUSIONS: The TC dyes exhibited high co-localization coefficients (>95%) and moderate quantum yields. They showed high biocompatibility and long-term retention, important features for biological applications. GENERAL SIGNIFICANCE: The results of the present work disclose a new class of organic dyes with potential wide applications as specific and efficient lysosome probes in the study of various biological processes.

[1]Benzothieno[3,2-b]benzothiophene-Based Organic Dyes for Dye-Sensitized Solar Cells.

Three new metal-free organic dyes with the [1]benzothieno[3,2-b]benzothiophene (BTBT) π-bridge, having the structure donor-π-acceptor (D-π-A) and labeled as 19, 20 and 21, have been designed and synthesized for application in dye-sensitized solar cells (DSSC). Once the design of the π-acceptor block was fixed, containing the BTBT as the π-bridge and the cyanoacrylic group as the electron acceptor and anchoring unit, we selected three donor units with different electron-donor capacity, in order to assemble new chromophores with high molar extinction coefficients (ε), whose absorption features well reflect the good performance of the final DSSC devices. Starting with the 19 dye, which shows a molar extinction coefficient ε of over 14,000 M(-1) cm(-1) and takes into account the absorption maximun at the longer wavelength, the substitution of the BFT donor unit with the BFA yields a great enhancement of absorptivity (molar extinction coefficient ε > 42,000 M(-1) cm(-1)), until reaching the higher value (ε > 69,000 M(-1) cm(-1)) with the BFPhz donor unit. The good general photovoltaic performances obtained with the three dyes highlight the suitable properties of electron-transport of the BTBT as the π-bridge in organic chromophore for DSSC, making this very cheap and easy to synthesize molecule particularly attractive for efficient and low-cost photovoltaic devices.

Exploiting Photo- and Electroluminescence Properties of FIrpic Organic Crystals.

In this work, we investigate the optical and structural properties of the well-known triplet emitter bis(4',6'-difluorophenylpyridinato)-iridium(III) picolinate (FIrpic), showing that its ability to pack in two different ordered crystal structures promotes attractive photophysical properties that are useful for solid-state lighting applications. This approach allows the detrimental effects of the nonradiative pathways on the luminescence performance in highly concentrated organic active materials to be weakened. The remarkable electro-optical behavior of sky-blue phosphorescent organic light-emitting diodes incorporating crystal domains of FIrpic, dispersed into an appropriate matrix as an active layer, has also been reported as well as the X-ray diffraction, nuclear magnetic resonance, electro-ionization mass spectrometry, and scanning electron microscopy analyses of the crystalline samples. We consider this result as a crucial starting point for further research aimed at the use of a crystal triplet emitter in optoelectronic devices to overcome the long-standing issue of luminescence self-quenching.

Thymol-Nanoparticles as Effective Biocides against the Quarantine Pathogen Xylella fastidiosa.

Quarantine pathogens require the investigation of new tools for effective plant protection. In particular, research on sustainable agrochemicals is the actual challenge. Plant extracts, essential oils, and gels are natural sources of efficient biocides, such as aromatic secondary metabolites. Thymol is the major phenolic constituent of thyme and oregano essential oils, and it can inhibit many pathogenic microbes. Thymol nanoparticles were obtained through adsorption on CaCO3 nanocrystals, exploiting their carrier action. High loading efficiency and capability were reached as verified through UV and TGA measurements. We report the first study of thymol effect on Xylella fastidiosa, conducing both fluorometric assay and in vitro inhibition assay. The first test confirmed the great antibacterial effect of this compound. Finally, an in vitro test revealed an interesting synergistic action of thymol and nanocarriers, suggesting the potential application of thymol-nanoparticles as effective biocides to control Xylella fastidiosa infection.

Synthesis of a light-responsive platinum curcumin complex, chemical and biological investigations and delivery to tumor cells by means of polymeric nanoparticles.

Platinum-based anticancer drugs are common in chemotherapy, but problems such as systemic toxicity and acquired resistance of some tumors hamper their clinical applications and therapeutic efficacy. It is necessary to synthesize Pt-based drugs and explore strategies to reduce side effects and improve pharmacokinetic profiles. Photo-responsive chemotherapeutics have emerged as an alternative strategy against several cancers, as photoactivation offers spatial selectivity and fewer side effects. Here, we combine chemical synthesis and nanotechnology to create a multifunctional platinum drug delivery system based on the novel metal complex [Pt(ppy)(curc)] (ppy = deprotonated 2-phenylpyridine, curc = deprotonated curcumin)] embodying the naturally occurring bioactive molecule, curcumin. The ultrasonication method coupled with the layer-by-layer technology was employed to produce nanocolloids, which demonstrated a good biocompatibility, higher solubility in aqueous solution, stability, large drug loading, and good biological activity in comparison with the free drug. In vitro release experiments revealed that the polymeric nanoformulation is relatively stable under physiological conditions (pH = 7.4 and 37 °C) but sensitive to acidic environments (pH = 5.6 and 37 °C) which would trigger the release of the loaded drug. Our approach modifies the bioavailability of this Pt-based drug increasing its therapeutic action in terms of both cytotoxic and anti-metastasis effects.

Low-Intensity Light-Responsive Anticancer Activity of Platinum(II) Complex Nanocolloids on 2D and 3D In Vitro Cancer Cell Model.

This study aimed to evaluate the therapeutic efficacy of low-intensity visible light responsive nanocolloids of a Pt-based drug using a 2D and three-dimensional (3D) in vitro cancer cell model. Biocompatible and biodegradable polymeric nanocolloids, obtained using the ultrasonication method coupled with Layer by Layer technology, were characterized in terms of size (100 ± 20 nm), physical stability, drug loading (78%), and photoactivation through spectroscopy studies. The in vitro biological effects were assessed in terms of efficacy, apoptosis induction, and DNA-Pt adducts formation. Biological experiments were performed both in dark and under visible light irradiation conditions, exploiting the complex photochemical properties. The light-stimuli responsive nanoformulation gave a significant enhancement in drug bioactivity. This allowed us to achieve satisfying results by using nanomolar drug concentration (50 nM), which was ineffective in darkness condition. Furthermore, our nanocolloids were validated in 3D in vitro spheroids using confocal microscopy and cytofluorimetric assay to compare their behavior on culture in 2D monolayers. The obtained results confirmed that these nanocolloids are promising tools for delivering Pt-based drugs.

Enhanced Bioactivity of Pomegranate Peel Extract following Controlled Release from CaCO3 Nanocrystals.

Pomegranate peel extract is rich of interesting bioactive chemicals, principally phenolic compounds, which have shown antimicrobial, anticancer, and antioxidative properties. The aim of this work was to improve extract' bioactivity through the adsorption on calcium carbonate nanocrystals. Nanocrystals revealed as efficient tools for extract adsorption reaching 50% of loading efficiency. Controlled release of the contained metabolites under acidic pH has been found, as it was confirmed by quantitative assay and qualitative study through NMR analysis. Specific functionality of inorganic nanocarriers could be also tuned by biopolymeric coating. The resulting coated nanoformulations showed a great antimicrobial activity against B. cinerea fungus preventing strawberries disease better than a commercial fungicide. Furthermore, nanoformulations demonstrated a good antiproliferative activity in neuroblastoma and breast cancer cells carrying out a higher cytotoxic effect respect to free extract, confirming a crucial role of nanocarriers. Finally, pomegranate peel extract showed a very high radical scavenging ability, equal to ascorbic acid. Antioxidant activity, measured also in intracellular environment, highlighted a protective action of extract-adsorbed nanocrystals twice than free extract, providing a possible application for new nutraceutical formulations.

Experimental data regarding the effects of urea addition into liquid fuel to combustion enhancement of a low NOx gas turbine combustor.

The article presents the data regarding the experimental characterization of combustion of liquid jet A1 with addition of urea-water emulsion. A liquid-fuel gas turbine derived burner operating in non-premixed mode under three different equivalence fuel/air ratios was used. The data were collected, with and without urea addition, with two high speed visualization systems which acquired the broadband and spatially and spectrally resolved chemiluminescence emissions. Chemiluminescence images of OH* were acquired using an intensified camera system with a narrow-band filter at approximately 310 nm CWL, while the chemiluminescence images of CH* were recorded with a 436 nm CWL. Measurements of exhaust temperature and NOx, CO and CO2 emissions have been also performed. The data presented here are related to the article entitled "COMBUSTION PERFORMANCE OF A LOW NOx GAS TURBINE COMBUSTOR USING UREA ADDITION INTO LIQUID FUEL" [1].

HPLC-HRMS Global Metabolomics Approach for the Diagnosis of "Olive Quick Decline Syndrome" Markers in Olive Trees Leaves.

Olive quick decline syndrome (OQDS) is a multifactorial disease affecting olive plants. The onset of this economically devastating disease has been associated with a Gram-negative plant pathogen called Xylella fastidiosa (Xf). Liquid chromatography separation coupled to high-resolution mass spectrometry detection is one the most widely applied technologies in metabolomics, as it provides a blend of rapid, sensitive, and selective qualitative and quantitative analyses with the ability to identify metabolites. The purpose of this work is the development of a global metabolomics mass spectrometry assay able to identify OQDS molecular markers that could discriminate between healthy (HP) and infected (OP) olive tree leaves. Results obtained via multivariate analysis through an HPLC-ESI HRMS platform (LTQ-Orbitrap from Thermo Scientific) show a clear separation between HP and OP samples. Among the differentially expressed metabolites, 18 different organic compounds highly expressed in the OP group were annotated; results obtained by this metabolomic approach could be used as a fast and reliable method for the biochemical characterization of OQDS and to develop targeted MS approaches for OQDS detection by foliage analysis.

Sonication-Assisted Production of Fosetyl-Al Nanocrystals: Investigation of Human Toxicity and In Vitro Antibacterial Efficacy against Xylella Fastidiosa.

Recently, there is a growing demand in sustainable phytopathogens control research. Nanotechnology provides several tools such as new pesticides formulations, antibacterial nanomaterials and smart delivery systems. Metal nano-oxides and different biopolymers have been exploited in order to develop nanopesticides which can offer a targeted solution minimizing side effects on environment and human health. This work proposed a nanotechnological approach to obtain a new formulation of systemic fungicide fosetyl-Al employing ultrasonication assisted production of water dispersible nanocrystals. Moreover, chitosan was applicated as a coating agent aiming a synergistic antimicrobial effect between biopolymer and fungicide. Fosetyl-Al nanocrystals have been characterized by morphological and physical-chemical analysis. Nanotoxicological investigation was carried out on human keratinocytes cells through cells viability test and ultrastructural analysis. In vitro planktonic growth, biofilm production and agar dilution assays have been conducted on two Xylella fastidiosa subspecies. Fosetyl-Al nanocrystals resulted very stable over time and less toxic respect to conventional formulation. Finally, chitosan-based fosetyl-Al nanocrystals showed an interesting antibacterial activity against Xylella fastidiosa subsp. pauca and Xylella fastidiosa subsp. fastidiosa.

Visible Light-Activated Water-Soluble Platicur Nanocolloids: Photocytotoxicity and Metabolomics Studies in Cancer Cells.

Nanoparticle-based drug delivery systems for cancer therapy offer a great promising opportunity as they specifically target cancer cells, also increasing the bioavailability of anticancer drugs characterized by low water solubility. Platicur, [Pt(cur) (NH3)2](NO3), is a cis-diamine-platinum(II) complex linked to curcumin. In this work, an ultrasonication method, coupled with layer by layer technology, allows us to obtain highly aqueous stable Platicur nanocolloids of about 100 nm. The visible light-activated Platicur nanocolloids showed an increased drug release and antitumor activity on HeLa cells, with respect to Platicur nanocolloids in darkness. This occurrence could give very interesting insight into selective activation of the nanodelivered Pt(II) complex and possible side-effect lowering. For the first time, the metabolic effects of Platicur nanocolloid photoactivation, in the HeLa cell line, have been investigated using an NMR-based metabolomics approach coupled with statistical multivariate data analysis. The reported results highlight specific metabolic differences between photoactivated and non-photoactivated Platicur NC-treated HeLa cancer cells.

Insights into the role of the lead/surfactant ratio in the formation and passivation of cesium lead bromide perovskite nanocrystals.

This study aims at rationalizing the effects of the lead/surfactant ratio on the structural evolution of cesium lead-bromide perovskite nanocrystals (NCs), ascertaining how their shape and surface composition can be modulated by suitably adjusting the ligand amount (an equivolumetric mixture of oleic acid and oleyl amine) relatively to lead bromide. The tailoring of the reaction conditions allows the obtainment of blue-emitting CsPbBr3 nanoplatelets in the presence of ligand excess, while green-emitting nanocubes are achieved under low-surfactant conditions. An insight into the NC's shape evolution dictated by the different reaction conditions suggests that the generation of CsPbBr3 nanoplatelets is controlled by the dimensions of [(RNH3)2(PbBr4)]n layers formed before the injection of cesium oleate. The growth step promoted by preformed layers is concomitant to (but independent from) the nucleation process of lead-based species, leading to centrosymmetric nanocubes (prevalent in low-surfactant regimes) or Cs4PbBr6 NCs (prevalent in high-surfactant regimes). The proposed NC growth is supported by the analysis of the optical properties of non-purified samples, which reveal the selective presence of structures endowed with four cell unit average thickness accompanying larger emissive nanocubes. By combining nuclear magnetic resonance (NMR) and UV-Vis spectroscopy techniques, it is ascertained that the lead/surfactant ratio also controls the relative proportion between lead-based species (PBr2, PbBr3-, PbBr42- and plausibly PbBr53- or PbBr64-) formed before cesium injection, which regulate the size of [(RNH3)2(PbBr4)]n layers as well as the formation of Cs4PbBr6 NCs during the nucleation stage. The surface chemistry of the differently structured perovskite NCs is investigated by correlating the elemental composition of the nanoparticles with specific NMR signals ascribable to the surface ligands. This level of investigation also sheds light on the stability of the time-dependent fluorescence exhibited by differently composed perovskite NCs before the loss of their colloidal integrity. Our findings can bring about a fine tuning of the synthetic methods currently employed for controlling the shape and surface chemistry of perovskite NCs.

CaCO3 as an Environmentally Friendly Renewable Material for Drug Delivery Systems: Uptake of HSA-CaCO3 Nanocrystals Conjugates in Cancer Cell Lines.

Chemical and biochemical functionalization of nanoparticles (NPs) can lead to an active cellular uptake enhancing their efficacy thanks to the targeted localization in tumors. In the present study calcium carbonate nano-crystals (CCNs), stabilized by an alcohol dehydration method, were successfully modified by grafting human serum albumin (HSA) on the surface to obtain a pure protein corona. Two types of CCNs were used: naked CaCO3 and the (3-aminopropyl)triethoxysilane (APTES) modified CaCO3-NH2. The HSA conjugation with naked CCN and amino-functionalized CCN (CCN-NH2) was established through the investigation of modification in size, zeta potential, and morphology by Transmission Electron Microscopy (TEM). The amount of HSA coating on the CCNs surface was assessed by spectrophotometry. Thermogravimetric analysis (TGA) and Differential scanning calorimetry (DSC) confirmed the grafting of APTES to the surface and successive adsorption of HSA. Furthermore, to evaluate the effect of protein complexation of CCNs on cellular behavior, bioavailability, and biological responses, three human model cancer cell lines, breast cancer (MCF7), cervical cancer (HeLa), and colon carcinoma (Caco-2) were selected to characterize the internalization kinetics, localization, and bio-interaction of the protein-enclosed CCNs. To monitor internalization of the various conjugates, chemical modification with fluorescein-isothiocyanate (FITC) was performed, and their stability over time was measured. Confocal microscopy was used to probe the uptake and confirm localization in the perinuclear region of the cancer cells. Flow cytometry assays confirmed that the bio-functionalization influence cellular uptake and the CCNs behavior depends on both cell line and surface features.

Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma.

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration.