pH-Sensitive Hybrid System Based on Eu3+/Gd3+ Co-Doped Hydroxyapatite and Mesoporous Silica Designed for Theranostic Applications.

Nanomaterials such as pH-responsive polymers are promising for targeted drug delivery systems, due to the difference in pH between tumor and healthy regions. However, there is a significant concern about the application of these materials in this field due to their low mechanical resistance, which can be attenuated by combining these polymers with mechanically resistant inorganic materials such as mesoporous silica nanoparticles (MSN) and hydroxyapatite (HA). Mesoporous silica has interesting properties such as high surface area and hydroxyapatite has been widely studied to aid in bone regeneration, providing special properties adding multifunctionality to the system. Furthermore, fields of medicine involving luminescent elements such as rare earth elements are an interesting option in cancer treatment. The present work aims to obtain a pH-sensitive hybrid system based on silica and hydroxyapatite with photoluminescent and magnetic properties. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), nitrogen adsorption methods, CHN elemental analysis, Zeta Potential, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), vibrational sample magnetometry (VSM), and photoluminescence analysis. Incorporation and release studies of the antitumor drug doxorubicin were performed to evaluate the potential use of these systems in targeted drug delivery. The results showed the luminescent and magnetic properties of the materials and showed suitable characteristics for application in the release of pH-sensitive drugs.

Boron nitride nanotubes for extraction of angiotensin receptor blockers from human plasma.

The limitations of silica-based sorbents boosted the development of new extraction phases. In this study, boron nitride nanotubes functionalized with octadecyl groups were used for the first time as sorbent for extraction of losartan and valsartan, the most used angiotensin receptor blockers in the clinical practice, from human plasma. The nanotubes were synthesized using the chemical vapor deposition technique, purified by acid treatment, functionalized with octadecylamine in a microwave reactor, and characterized by different techniques. The functionalized nanotubes were packed in solid phase extraction cartridges. Extraction conditions were optimized by means of a 23 factorial design with center points. The separation was performed on a biphenyl core-shell (100 × 4.6 mm; 2.6 µm) column, using 0.1 % (v/v) triethylamine solution and methanol (pH 3.2) as mobile phase, at 0.7 mL/min, in gradient elution. The injection volume was 10 µL and fluorescence detection was performed at excitation and emission wavelengths of 250 and 375 nm, respectively. The developed method was validated according to Brazilian Health Regulatory Agency (ANVISA), United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) guidelines and presented selectivity, precision, accuracy, and linearity in the concentration ranges of 50-1200 ng/mL for losartan and 20-1700 ng/mL for valsartan. Recoveries higher than 80 % were obtained. The method was fit for the quantification of losartan in plasma samples from patients under antihypertensive therapy, being useful in therapeutic drug monitoring, pharmacokinetics and bioequivalence studies.

Synthesis and characterization of gold nanorods coated by mesoporous silica MCM-41 as a platform bioapplication in photohyperthermia.

Gold nanoparticles have been widely investigated for biomedical applications due to their optical properties. These particles present the interesting feature of absorbing light when stimulated with laser radiation to generate heating. Among the possible morphologies for synthetic gold nanoparticles, gold nanorods have properties of great interest for applications in the photohyperthermia processes. Due to their morphology, gold nanorods can absorb light at longer wavelengths comprising specific regions of the electromagnetic spectrum, such as the region of the biological window, in which laser radiation has less interaction with tissues. However, these nanoparticles present limitations in biomedical applications, such as low colloidal and thermal stabilities that can be overcome by coating the gold nanorods with silica MCM-41. The silicate covering can provide greater stability for gold nanorods and allow multifunctionality in treating different diseases through photohyperthermia. This work developed a specific chemical route through seed and growth solutions to synthesize gold nanorods with controlled particle size, rod morphology, and silica covering for photohyperthermia applications. The synthesized samples were characterized through a multi-technique approach that successfully demonstrated the presence of gold nanorods inside the silica coating, presenting high stability and desirable textural and morphological characteristics for bioapplications. Furthermore, silica-coated gold nanorods exhibit high biocompatibility and great performance in generating therapeutic heating by absorbing laser radiation in the biological window range, making the system developed in this work a promising agent in photohyperthermia.

Boron nitride nanotubes radiolabeled with 153Sm and 159Gd: Potential application in nanomedicine.

Boron nitride nanotubes (BNNTs) have been growing in notoriety in the development of systems aiming bioapplications. In this work we conducted an investigation about the mechanisms involved in the incorporation of samarium and gadolinium in BNNTs. The process was performed by the reduction of samarium and gadolinium oxides (Sm2O3 and Gd2O3, respectively) in the presence of NH3 gas (witch decomposes into N2 and H2) at high temperatures. Various characterization techniques were conducted to elucidate how Sm and Gd are introduced into the BNNT structure. Biological in vitro assays were performed with human fibroblasts and a human osteosarcoma cell line (SAOS-2). Our results show that the studied systems have high potential for biomedical application and can be used as non-invasive imaging agents, such as scintigraphy radiotracers or as magnetic resonance imaging (MRI) contrast medium, being able to promote the treatment of many types of tumors simultaneously to their diagnosis.

Protection of normal cells from irradiation bystander effects by silica-flufenamic acid nanoparticles.

The development of a myriad of nanoparticles types has opened new possibilities for the diagnostics and treatment of many diseases, especially for cancer. However, most of the researches done so far do not focus on the protection of normal cells surrounding a tumor from irradiation bystander effects that might lead to cancer recurrence. Gap-junctions are known to be involved in this process, which leads to genomic instability of neighboring normal cells, and flufenamic acid (FFA) is included in a new group of gap-junction blockers recently discovered. The present work explores the use of mesoporous silica nanoparticles MCM-41 functionalized with 3-Aminopropyltriethoxysilane (APTES) for anchoring the flufenamic acid for its prolonged and controlled release and protection from radiation bystander effects. MCM-41 and functionalized samples were structurally and chemically characterized with multiple techniques. The biocompatibility of all samples was tested in a live/dead assay performed in cultured MRC-5 and HeLa cells. HeLa cells cultured were exposed to 50 Gy of gamma-rays and the media transferred to fibroblast cells cultured separately. Our results show that MCM-41 and functionalized samples have high biocompatibility with MCR-5 and HeLa cells, and most importantly, the FFA delivered by these NPs was able to halt apoptosis, one of main bystander effects.

Synthesis and Characterization of Poly(N-isopropylacrylamide)/SBA-15 Silica Nanocomposites.

The combination of the mesoporous silica material SBA-1 5 with the temperature-responsive hydrogels, such as poly(N-isopropylacrylamide) P(N-iPAAm) can lead to the formation of a material with the potential for application as a new drug delivery system, given that self-regulated delivery allows for drug release when needed. The present work studies the synthesis and characterization of hybrid systems consisting of the poly(N-isopropylacrylamide) hydrogel and SBA-15 by varying the amount of hydrogel within the silica network. A systematic study on the structural properties of hybrid samples, their thermal stability and the degradation of the polymer chains in silica was carried out through characterization techniques, including SAXS, thermogravimetry and physical adsorption of N2. The results were critically examined and compared with pure SBA-15. The present study's results demonstrated that the thermosensibility of P(N-iPAAm) was retained in the hybrid system, which presented a low critical solution temperature, similar to that of pure P(N-iPAAm). Moreover, the hydrogel did not fully occupy the available intrachannel space, making the [SBA-15/P(N-iPAAm)] hybrids a very promising candidate for hosting and further delivery, under appropriate conditions, of a variety of molecules of pharmaceutical interest.

An in situ synthesis of mesoporous SBA-16/hydroxyapatite for ciprofloxacin release: in vitro stability and cytocompatibility studies.

The present work developed a biomaterial (HA/SBA-16) based on the growth of calcium phosphate (HA) particles within an organized silica structure (SBA-16) to evaluate its application as a drug delivery system. The samples were charged with ciprofloxacin as a model drug and in vitro release assays were carried out. The samples were characterized by elemental analysis (CHN), Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), small angle X-ray scattering (SAXS) and X-ray diffraction. The results obtained by TEM, SEM and SAXS reveal a well-defined cubic arrangement of a uniform spherical mesoporous structure, an intrinsic characteristic of these materials, which indicated that SBA-16 and HA/SBA-16 could potentially encapsulate bioactive molecules by means of ordered mesopores. It was found that both surface interaction and pore volume affect the rate and amount of ciprofloxacin released from the mesoporous materials. In vitro assays were performed to evaluate the adhesion, viability, and growth behavior of human adipose tissue-derived stem cells (hADSC) on SBA-16 and HA/SBA-16 nanocomposites to verify their potential as a scaffold for application in bone-tissue engineering using MTT assay and alkaline phosphatase activity tests. The results showed that the materials are promising systems for bone repair, providing a good environment for the adhesion and proliferation of rat mesenchymal stem cells and hADSC in vitro.

Magnetic solid-phase extraction based on mesoporous silica-coated magnetic nanoparticles for analysis of oral antidiabetic drugs in human plasma.

In the present work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation-precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The mesoporous SiO2-coated Fe3O4 samples were functionalized using octadecyltrimethoxysilane as silanizing agent. The pure and functionalized silica nanoparticles were physicochemically and morphologically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N2 adsorption, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The resultant magnetic silica nanoparticles were applied as sorbents for magnetic solid-phase extraction (MSPE) of oral antidiabetic drugs in human plasma. Our results revealed that the magnetite nanoparticles were completely coated by well-ordered mesoporous silica with free pores and stable pore walls, and that the structural and magnetic properties of the Fe3O4 nanoparticles were preserved in the applied synthesis route. Indeed, the sorbent material was capable of extracting the antidiabetic drugs from human plasma, being useful for the sample preparation in biological matrices.

Boron nitride nanotubes coated with organic hydrophilic agents: stability and cytocompatibility studies.

In the present study, Boron Nitride Nanotubes (BNNTs) were synthesized and functionalized with organic hydrophilic agents constituted by glucosamine (GA), polyethylene glycol (PEG)1000, and chitosan (CH) forming new singular systems. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy, while their surface charge was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by Transmission Electron Microscopy. The functionalization was evaluated by Thermogravimetry analysis and Fourier Transformer Infrared Spectroscopy. The results showed that BNNTs were successfully obtained and functionalized, reaching a mean size and dispersity deemed adequate for in vitro studies. The in vitro stability tests also revealed a good adhesion of functionalized agents on BNNT surfaces. Finally, the in vitro cytocompatibility of functionalized BNNTs against MCR-5 cells was evaluated, and the results revealed that none of the different functionalization agents disturbed the propagation of normal cells up to the concentration of 50 µg/mL. Furthermore, in this concentration, no significantly chromosomal or morphologic alterations or increase in ROS (Reactive Oxygen Species) could be observed. Thus, findings from the present study reveal an important stability and cytocompatibility of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.

Boron nitride nanotubes radiolabeled with 99mTc: preparation, physicochemical characterization, biodistribution study, and scintigraphic imaging in Swiss mice.

In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy (PCS), while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by scanning electron microscopy (SEM). The functionalization in the nanotubes was evaluated by thermogravimetry analysis (TGA) and Fourier transformer infrared spectroscopy. The results showed that BNNTs were obtained and functionalized successfully, reaching a mean size and dispersity deemed adequate for in vivo studies. The BNNTs were also evaluated by ex vivo biodistribution studies and scintigraphic imaging in healthy mice. The results showed that nanostructures, after 24h, having accumulated in the liver, spleen and gut, and eliminated via renal excretion. The findings from this study reveal a potential application of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.