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In this work, silica-based adsorbents were prepared by a facile and straightforward sol–gel route. The adsorption capacity of the prepared materials was investigated using methylene blue (MB) and metamizole (sodium dipyrone – DIP) as reference pollutants. We observed that the samples prepared here, regardless of the absence of catalyst, templating agent, or heat treatment step during their preparation, are promising materials for adsorption purposes. The adsorption kinetics was investigated based on the pseudo-first and pseudo-second-order kinetic laws of Lagergren. The most promising sample showed an adsorption capacity of 36.9 mg g−1 (removal capacity of 92.3%) for MB and 8.5 mg g−1 (20.5%) for DIP in aqueous media kept at a pH = 7.0. We observed that the adsorption of these species is strongly associated with the electrostatic interaction between the pollutant molecules and the silica surface. Such an interaction was increased when the pH of the solution increased from 3.0 to 4.5, 7.0, or 9.0. The incorporation of amino groups derived from (3-Aminopropyl)triethoxysilane (APTES) increased the affinity of silica for MB and DIP. These functional groups were incorporated into silica via post-grafting and co-condensation. Furthermore, it was shown that the silica matrices tested here can be easily regenerated by heat treatment in air at 450 °C for periods as short as 15 min, allowing its reuse in subsequent adsorption cycles.

In this study, phosphate-buffered saline solution (PBS) was successfully radiolabeled with technetium-99m. The biodistribution profile and bone accumulation of the [99mTc]Tc-PBS system were evaluated in healthy swiss mice. The radiolabeling of the system was successfully obtained, yielding around 90 % of radiochemical purity. The system stability was tested in the presence of saline medium at 25 oC and mouse plasma at 37 oC, and results revealed that [99mTc]Tc-PBS showed excellent stability over time, in both media. It was observed a biphasic clearance profile, with fast elimination from the bloodstream by renal filtration. The radiolabeled system revealed a high specificity bone accumulation was observed, demonstrating an uptake behavior from 20 to 50 times higher than muscle, used as control. From all results obtained, the system constituted by [99mTc]Tc-PBS can be considered a potential selective agent for bone imaging.

Several colloidal nanosystems have been developed aiming biomedical applications that include investigations related to magnetic resonance imaging (MRI) procedures. In this work, a core-shell structure consisting of iron oxide nanoparticles (IONPs) nucleus grafted with polyethylene glycol (PEG)4000 was prepared and evaluated by physicochemical and magnetic characterization. The polymer was covalently immobilized over nanoparticles through a simple and rapid in situ chemical method. The resulting hybrid material was capable of inducing a relevant T2 relaxation time in an average compared to marketed MRI formulations, revealing both physical characteristics and magnetic properties adequate for MRI applications. Furthermore, the in vitro biocompatibility profile was assessed by flow cytometry technique, using healthy human cell lineage (HEK-293). The results indicated good biocompatibility profile and non-anti-proliferative properties, and therefore, IONP-PEG can be considered as a new system candidate as a T2 contrast agent for MRI applications.

Responsive polymers are a promising class of materials for a variety of applications, especially for the construction of biomedical devices such as novel drug delivery systems. In this work, we describe the synthesis of thermoresponsive protein-polymer conjugates with a phase-transition slightly higher than physiological temperature. Such conjugates could enable targeted drug delivery through the bloodstream with aggregation and accumulation at cancer tissue. Random copolymers composed of N-vinylcaprolactam (NVCL) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) were grafted from bovine serum albumin (BSA) by Cu(0)-mediated radical polymerization. The obtained BSA-P(NVCL0.7-co-DMAEMA0.3) conjugates are, to the best of our knowledge, the first example of protein-polymer conjugates with PNVCL and revealed a cloud point around 40 °C. Furthermore, these conjugates were evaluated for their suitability as drug delivery vehicles for the anti-cancer drug cisplatin which still causes serious side effects when used as a free drug. BSA is known to bind cisplatin and the synthesized conjugates revealed a high cisplatin loading capacity and a significant cytotoxic profile against human breast cancer cells. Thus, these new smart hybrid materials may serve as potential carriers for the delivery of drugs or other applications in the biomedical area, especially in the field of anti-cancer treatment.

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

Silver tungstate nanoparticles have been presenting attractive characteristics that could allow its usage in the biomedical sciences. In this study, Ag2WO4 nanoparticles with an average size of 242 nm were obtained and radiolabeled with technetium-99m with high labeling-yield as well as high stability. Biodistribution studies were carried out in healthy and tumor-bearing mice to determine the nanoparticle’s in vivo behavior. The results revealed an important tumor-to-muscle ratio, reaching values above than 1.5, demonstrated the ability of this nanomaterial in accumulating preferentially in tumor tissue. All results together, converge to consider the Ag2WO4 nanoparticles as a potential system against cancer and a potential new radiolabeled probe for tumor identification and uptake.

Polyhydroxyalkanoates (PHAs) are often used for fabrication of biocompatible and absorbable medical devices due to their high biocompatibility and biodegradability. Among them, poly (-3-hydroxybutyrate) (PHB) and Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are the most studied members of the PHA family, with numerous applications, especially in the biomedical areas. Due to superior physicochemical characteristics, in biological medium, PHBV degrades at a slower rate than PHB, making the copolymer an interesting long-term drug release platform, for example, encapsulating antineoplastic drugs for cancer therapy. Papers describing the use of PHBV-based nanoparticles for tumor have been dedicated to passive targeting-strategies based on the EPR effect and the results have been revealed relevant outcomes in cancer research. From the relevant advances obtained in the last years, this review focuses on the ultimate progresses obtained by PHBV systems on the cellular uptake knowledge, biocompatibility and applications in tumor targeting, took into account on the latest advances related to new strategies to obtain nanostructured systems through the living radical polymerization methodologies, aiming to bring a relevant update regarding biomedical applications of PHBV.

Single-walled carbon nanotubes (SWCNT) are raising interest in biomedical field, as a drug delivery system, due to their large payload capacity and rich surface chemistry that allows attaching molecules. Generally, carbon nanotubes, without any surface modifications are cytotoxic to certain mammalian cells. However, after their functionalization, they become biocompatible and non-immunogenic. Thus, the aim of this work was to evaluate the effect of functionalization groups on the biocompatibility of SWCNT in vitro, as well as on its biodistribution in tumor-bearing mice. In this approach, carboxylate and bisphosphonate functionalized SWCNT were successfully synthesized and characterized by Raman, FTIR, and TGA techniques. The in vitro cytotoxicity against HEK-293 cells, and hemolysis assay were carried out and the results revealed important biocompatibility profile for both functionalized nanotubes. Furthermore, both types of SWCNT were successful radiolabeled with technetium-99 m, and biodistribution studies were conducted in Ehrlich tumor-bearing Swiss mice, showing higher tumor uptake by bisphosphonated SWCNT compared to carboxylated nanotubes. Moreover, acute toxicity study was performed in healthy Swiss mice revealing that none of the nanotubes displayed hematological, hepatic or renal toxicity. From all obtained results, the bisphosphonate functionalized SWCNT can be considered a plausible and alternative drug delivery platform for theranostic and therapeutics purposes.

Nanostructured polymer blends exhibit better properties over bulk polymeric blends and their homopolymers since several properties, such as stability, tensile strength, ductility, transparency, cre...

The Internet-of-Things (IoT) has transformed everyday manual tasks into digital and automatable ones, giving way to the birth of several end-user development solutions that attempt to ease the task of configuring and automating IoT systems without requiring prior technical knowledge. While some studies reflect on the automation rules that end-users choose to program into their spaces, they are limited by the number of devices and possible rules that the tool under study supports. There is a lack of systematic research on (1) the automation rules that users wish to configure on their homes, (2) the different ways users state their intents, and (3) the complexity of the rules themselves—without the limitations imposed by specific IoT devices systems and end-user development tools. This paper surveyed twenty participants about home automation rules given a standard house model and device’s list, without limiting their creativity and resulting automation complexity. We analyzed and systematized the collected 177 scenarios into seven different interaction categories, representing the most common smart home interactions.

Protein-polymer conjugates have achieved tremendous attention in the last few years, since their importance in diverse fields including drug delivery, biotechnology and nanotechnology. Over the past few years, numerous chemical strategies have been developed to conjugate different synthetic polymers onto proteins and great progress has been made. Currently, there are a handful of therapeutic polymer conjugates that have been approved by the FDA, while many hundreds of products are under extensive clinical trials and preclinical development phases. In this way, the development of novel techniques for conjugation, especially living radical polymerisation (LRP) has greatly enhanced the potential to broaden the scope of therapeutic conjugates. As a consequence, versatile techniques have developed, such as the 'grafting from' approach, which allows modifications of biomacromolecules at the atomic level, and subsequently preparing well-defined stimuli-responsive conjugates. These strategies present a unique perspective for therapy expansion of a new generation of 'smart' products with proprieties that can be finely controlled and tuned rather than just enhanced. This article highlights recent advances in the synthesis and application of protein-polymer conjugates by controlled radical polymerisation techniques, with special emphasis on stimuli-responsive conjugates on new applications in biomedical and pharmaceutical areas.

Nanocarriers combining two or more different approaches in the same particle has been a new trend in research worldwide. Among the strategies studied, magnetic nanoparticles with dual properties related to drug delivery and diagnostic imaging represent a significant improvement in the response of chemotherapy and in a real-time monitoring of drug distribution. Nanocarriers combining dual properties such as thermal and magnetic, enable controlling the release and modulate a treatment giving more specificity of action. This is possible since a magnetic external field can allow the adequate movement of nanoparticles and provide a means to remotely heating the target tissue safely. The temperature increase can trigger changes in the structure of nanocarriers leading to the release of drugs. This field of study known as magnetic fluid hyperthermia (MFH), currently in order to improve the selective heating process has been used superparamagnetic nanostructured, mainly made up of iron oxide, coated or encapsulated in, mostly, polymeric nanoparticles. In this way, this review aims to provide an updated review of the state of art of nanostructured systems that combines simultaneously magnetic hyperthermia and thermal properties in the preclinical level investigation.

Angiogenesis, the complex process of formation of new blood vessels from pre-existing blood vessels, which involves the participation of several pro- and anti-angiogenic factors, is implicated in many physiological and pathological conditions. Nanoparticle-based anti-angiogenic activity at the tumour tissue, harnessed by the Enhanced Permeability and Retention Effect (EPR effect), could potentially become a breakthrough therapy to halt tumour progression. Herein, we evaluate the anti-angiogenic effect of ZnWO4 nanoparticles (NPs). The nanoparticles were obtained by microwave-assisted hydrothermal synthesis (MAHS) at 120 °C for 60 min and were structurally characterised by X-ray diffraction (XRD) and micro-Raman (MR) spectroscopy. The mean size and polydispersity index were estimated by Zeta potential analysis. The XRD analysis revealed structural organisation at a long-range order, with an average crystallite size of around 3.67 nm, while MR revealed short-range order for ZnWO4. The anti-angiogeni...

Airborne particulate matter (PM) is dispersed into the atmosphere and can internalize in the lungs during the respiratory process by passive exposure. Itabira city (Minas Gerais, Brazil) is a mining city with relevant PM emissions derived from iron exploitation, transport, and processing. In the present study, the PM2.5, PM10, and PM20 characterization from iron ore and its internalization and cytotoxicity effects were evaluated in the MRC-5 human lung cell line. PMs were characterized using scanning electron microscopy with EDS and X-ray analysis and, then, dispersed in water and analyzed by Dynamic Light Scattering and Nanosight techniques. Flow cytometry was applied to evaluate PM cellular uptake on MRC-5 cells and death induction. The results demonstrate that the PM10 mass collected were higher than those reported by the local governmental agencies and the PMs are mainly constituted by hematite and quartz. EDS analysis showed the presence of Fe, Si, Mg, Al, Zi, Ca, and emerging metallic contaminants, such as Ba and Ti, in environmental samples. Analyzed PM samples dissociate into nanoparticles (

Gadodiamide (Gd-DTPA-BMA) is a gadolinium-based complex, used as a contrast agent in magnetic resonance imaging procedures. Recent studies revealed the capacity of this complex of inducing apoptosis in neoplastic cells. However, a great challenge for its use as an anticancer drug is low cellular internalization and drug delivery systems such as thermosensitive liposomes can be a strategy to overcome these limitations and increase anti-tumor efficacy. In this context, this study aimed to develop, characterize, and assess the cytotoxic activity and selectivity index of thermosensitive liposomes containing Gd-DTPA-BMA. Formulations were prepared by the lipid film hydration method and their physicochemical, morphological, and thermal properties were evaluated. Cell viability was performed 4T1/MDA-MB-231 tumor cells and WI-26 VA4 normal cells. Transmission electron microscopy analyses showed high electron density in the inner core of Gd-DTPA-BMA-loaded liposomes that can be attributed to the Gd-DTPA-BMA, since Gd-loaded nanosystems present low light transmittance and high electron density by this technique. The dynamic light scattering, differential scanning calorimetry, small-angle X-ray scattering, and in vitro release results confirm that the lipid composition was suitable since Tc (temperature of the transition Lβ → Lα) values are in accordance with those reported for thermosensitive liposomes used in the treatment of cancer. The cytotoxic studies against breast cancer cell lines demonstrated that the Gd-DTPA-BMA-loaded liposomes have higher cytotoxicity than free Gd-DTPA-BMA. Moreover, these liposomes presented minimal toxicity in a normal cell line when compared to the free Gd-DTPA-BMA. Therefore, the results of this study suggest that thermosensitive liposomes containing Gd-DTPA-BMA might be a new promising nanocarrier system for breast cancer treatment.

Nowadays, infectious diseases are still a great challenge for human health. Bacterial infections are one of the primary causes of worldwide mortality. Due to the development of resistance processes, the search for therapeutic alternatives has focused on many researchers of biomedical areas. In this sense, antimicrobial drugs' encapsulation has emerged as a relevant alternative, capable of improving the therapeutic effectiveness, while a significant reduction in the side effects can be observed. Following in this same direction, in the present work, mesoporous iron oxide nanoparticles (MIONs), loaded with ciprofloxacin, were prepared, aiming to evaluate the system's potential application against bacterial infections. MIONs and silanized MIONs (MIONs@APTES) were prepared, presenting an average size below 100 nm and a superficial area of 258.27 and 186.27 m2 g−1, respectively. Both samples allowed to load relevant amounts of the drug, reaching a high incorporation rate and a controlled release profile, with different kinetics behavior, when incubated with simulated body fluid (SBF). The in vitro evaluation revealed that fabricated systems display biocompatible profiles over normal human cell lineage, where no significant cytotoxic profile was observed. However, it presented relevant antibiofilm (S aureus strain) properties when compared to controls constituted by free ciprofloxacin and nanoparticles without the drug. From all Results obtained in this work, the produced nanosystems can be considered a potential system to be applied in bacterial infection treatment.

Uncontrolled angiogenesis is directly associated with ocular diseases such as macular degeneration and diabetic retinopathy. Implantable polymeric drug delivery systems have been proposed for intravitreal applications and in the present work, we evaluated the antiangiogenic potential of PLGA ocular implants loaded with the triterpene lupeol using in vitro and in vivo models. The drug/polymer physiochemical properties of the lupeol-loaded PLGA were validated as functionally similar using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Interestingly, in an in vitro culture system, lupeol (100 μg/mL and 250 μg/mL) was capable to inhibited the proliferation as well as the migration of Human Umbilical Vein Endothelial Cells (HUVEC), without interfering in cell viability, promoting a significant reduction in the percentage of vessels (39.41% and 44.12%, respectively), compared with the control group. In vivo test, by using the chorioallantoic membrane (CAM) model, lupeol-loaded PLGA ocular implants showed antiangiogenic activity comparable to the FDA-approved anti-VEGF antibody Bevacizumab. Overall, our results suggest lupeol-loaded PLGA ocular implants were able to inhibit the angiogenic process by impairing both proliferation and migration of endothelial cells.

Nanostructured carriers with dual characteristics that combine two different approaches have been the object of intense research worldwide and constitute an interesting advance in research into procedures that aim to treat diseases and cancer. Some systems combine the use of two different drugs to treat cancer. Simultaneously, these drugs can act at different phases of the cell cycle aiming to arrest the cells’ growth after they developed chemoresistance. Other systems have combined the thermal and magnetic properties, seeking to obtain advantages on the control of the release kinetics or modulating a treatment, giving more specificity of action. As the temperature of the human body remains almost stable at 37°C, a slight local heating, observed in some pathological conditions such as inflammation and infection can represent an important opportunity to biomedical nanosystems for selective temperature-responsive release of their contents. The combination of both magnetic and thermal properties is often more suitable, as an external magnetic field can force align or move nanoparticles and provide an adequate means of remote heating in part of a tissue. Temperature can trigger a change in surface properties, modifying the size, water content, and diffusivity of radioisotopes. Still under the action of an adequate magnetic field, thermal-responsive and magnetic hybrid nanosystems can release, selectively, drugs and allow the separation/immobilization of proteins in specific sites. As organic-constituted nanomaterials are not suitable for magnetic applications, only hybrid systems (inorganic and organic) can be used in this approach. The present chapter aims to review the most recent advances in biomedical nanoparticle carriers that combine thermal and magnetic responses, detailing the mainly inorganic materials used as core and as well as the temperature-responsive polymers more commonly applied as an organic part of these new, hybrid, therapeutic nanosystems.

Molecules of the renin angiotensin-system have been received the attention of many scientists since recent works have revealed important antitumor activity. A heptapeptide with chemical similarity with Angiotensin [Ang-(1–7)], called Alamandine, showed in previously published works relevant biologic activities and in the present work, a potential nanomedicine formulation based on mesoporous silica nanoparticles loaded with Alamandine was prepared aiming to evaluate its potential application against cancer. SBA-16 and silanized-SBA-16 nanoparticles were synthesized and characterized, revealing a high Alamandine incorporation rate. Relevant cytotoxicity of the system was determined through the flow cytometry technique, over 4T1 (murine breast cancer) and A549 (human pulmonary cancer) cells. Furthermore, the system was crucial to reveal the antitumor capacity of alamandine, since it was observed a relevant reduction in the concentration necessary to conduct to death a significant number of tumor cells. From all results obtained, the present study suggests a new perspective on the use of Alamandine-MSNs as a novel nanomedicine for future applications in cancer treatment.

The Schistosoma mansoni is a parasite that is associated with several pathologies of great relevance to humans. Prophylactic and epidemiological strategies have been proposed in order to reduce the number of cases of infection. However, although chemotherapeutic drugs currently available may treat the disease, they are inefficient in preventing this illness. Thus, the development of vaccines against Schistosoma mansoni has great importance for diminishing the number of cases. To reach this goal, the search for new adjuvants is important to optimize the immunological response. In this scenario, nanostructured materials including mesoporous silica nanoparticles (MSN) have attracted much attention due to their high biocompatibility, chemical stability, biodegradability, and high payloads, thereby making them a promising candidate as a vaccine adjuvant. Therefore, the present work aimed to study the immune response generated by Soluble Worm Antigenic Preparation obtained from adult Schitosoma mansoni loaded in MSN as a potential vaccine against S. mansoni. MSN were characterized according to their size, zeta potential, and porosity, showing suitable characteristics for in vivo applications. SWAP was successfully incorporated into MSN and immune assays indicate that MSN are capable of stimulating high immune response, in comparison to conventional adjuvants. In conclusion, data presented in this work indicate the feasibility of SWAP-loaded MSN in stimulating the immune system of mice. The SWAP-loaded MSN might be considered a strategy to produce vaccines against S. mansoni.

Purpose This work studies the implications of different traffic patterns for heavy metal and solid pollution generation processes following rainfall events with contrasting antecedent meteorological conditions, at a periurban catchment. The aim is to provide information on the pollution processes and their potential environmental impacts for urban areas. Materials and methods Seven campaigns were performed covering winter, spring, and summer conditions, for rainfall events with different antecedent conditions. Four types of roads were monitored: low traffic, average traffic, heavy traffic with demanding driving situations (break and turning), and heavy traffic with high vehicle speed (motorway profile). Samples were taken at the beginning, middle and end of the events to measure within event variation in concentration. Analytical standard procedures were used to quantify pH, conductivity, turbidity, total solids, volatile solids, suspended solids, volatile suspended solids and heavy metals (Cd, Cu, Pb and Zn) in the total and dissolved forms (as to infer the particulate fraction), namely copper, zinc, cadmium and lead. Results and discussion The collected data show a direct relation among the number of vehicles and/or the driving manoeuvres performed by them and the amount of solids and heavy metals present in the wash out overland flow collected. An important fraction of the heavy metals is washed off in the particulate form, which represents an increased problem since the road overland flow is directed to green/brown areas and for the local aquatic ecosystems. Maximum copper values recorded exceed 0.6 mh L−1 , zinc exceeds 5 mg L−1 , lead 0.1 mg L−1 and cadmium 0.01 mg L−1 . Values are higher after long dry spells and reduce concentration throughout the rainfall events. Conclusions An important part of the heavy metals (with relevance for zinc and lead) are washed off in the particulate form, pollutants are typically related to the amount of traffic, and especially to the existence of driving manoeuvres. The summer events show the highest values, due to the accumulation of pollutants during the long dry spells. info:eu-repo/semantics/publishedVersion

Hydroxyapatite is used as a drug-delivery system for bone therapy applications because of its biocompatibility, bioactivity, and osteoconductive properties. In addition, hydroxyapatite nanoparticles (HApN) might be used as a theranostic probe. The aim of this study was to prepare and characterize hydroxyapatite mesoporous nanoparticles, and radiolabel these nanoparticles with technetium-99m (Tc). Moreover, biodistribution studies were carried out in healthy mice.HApN were synthesized and characterized. Tc-HApN was prepared by adding Tc-pertechnetate to a dispersion of HApN in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of Tc-HApN was determined by measuring blood radioactivity in healthy mice. In addition, biodistribution studies were carried out in healthy mice at 1 and 4 h after injection.Tc-HApN showed high radiochemical purity (98.7±0.2%) and in-vitro stability until 24 h. Tc-HApN levels in blood decreased in a biphasic manner, with an α half-life of 1.8 min and a β half-life of 126.9 min. High uptake was achieved in the liver and spleen because of the macrophage uptake. Furthermore, bone uptake was higher than that of the surrounding muscle, resulting in high bone-to-muscle ratios.HApN were synthesized successfully with suitable characteristics for in-vivo applications. Tc-HApN was prepared and showed high stability. Tc-HApN presented increasing bone uptake over time, showing a higher affinity to bone tissues in contrast to surrounding muscle. The present results, together with further studies, may indicate a potential application of HApN as a nanocarrier for bone diseases.

Theranostic nanosystems have attracted the attention of many scientists in worldwide due to its ability to accumulate and release selectively, in specific sites, compounds capable to generate images and to treat tumors, allowing simultaneously, the diagnose and treatment of cancer. Radioactive Gadolinium-159, a beta e gamma radiation emitter, has the properties to generate scintigraphic images and simultaneously, to conduct cancer cells to the death through high radiation doses. In this sense, the purpose of this study was to prepare PEG-coated and folate-PEG-coated long-circulating and pH-sensitive liposomes loaded with 159 Gd, and to evaluate the feasibility of these systems as theranostic probes in tumor-bearing mice. Liposomes were prepared by loading 159 Gd and Poly- l -Lysine, with a mean diameter of 120 nm in a monodisperse formulation. Scintigraphic images performed in Ehrlich tumor-bearing mice indicated that folate-coated liposome accumulation was more than 3-times higher than liposomes with no coating. Animals also showed higher survival rates when treated with folate-coated liposomes loaded with 159 Gd. Therefore, 159 Gd-FTSpHL improved the survival of the animals and showed higher tumor uptake, indicating that 159 Gd-FTSpHL possesses potential applications as a theranostic probe.

Nanostructured materials including mesoporous silica nanoparticles (MSNs) have attracted attention due to their recently discovered capability to increase the immune responses acting as an innovative vaccine adjuvant. Therefore, the present work aimed to study the potential use of mesoporous SBA-16 and silanized SBA-16 (APTES-SBA-16) nanoparticles as a vaccine adjuvant against the pathogenic fungus Paracoccidioides brasiliensis (PCM). In this sense, the antigenic protein rPb27 was incorporated into both mesoporous matrices. The synthesized nanomaterials were physicochemical and morphological characterized and the results obtained revealed consistent data with nanosized mesoporous nanoparticles in a monodisperse colloidal system. In the next step, the rPb27 antigen loading efficiency was evaluated using different ratios of nanoparticles/antigen and subsequently, the in vitro release kinetics was evaluated until 63 days. After, rPb27 was successfully radiolabeled with 99mTc and injected into thigh muscle of healthy mice in order to evaluate the in vivo release profile of rPb27 from nanoparticles to the bloodstream. The results revealed that APTES-SBA-16 matrix was capable to maintain a sustained release profile without insignificant cytotoxicity to normal human lineage cells. Altogether, these results suggest that APTES-SBA-16 nanoparticles can considered a potential adjuvant system for developing vaccines against the PCM.

Angiogenesis, the complex process of formation of new blood vessels from pre-existing blood vessels, which involves the participation of several pro- and anti-angiogenic factors, is implicated in many physiological and pathological conditions. Nanoparticle-based anti-angiogenic activity at the tumour tissue, harnessed by the Enhanced Permeability and Retention Effect (EPR effect), could potentially become a breakthrough therapy to halt tumour progression. Herein, we evaluate the anti-angiogenic effect of ZnWO

Gadodiamide (Gd-DTPA-BMA) is a gadolinium (Gd) chelate composed of two carboxylate groups of diethylenetriaminepentaacetic acid (DTPA) and two amide groups (BMA). Gd complexes are the most widely used contrast agents in nuclear magnetic resonance. Furthermore, our research group has demonstrated the potential of liposomes containing Gd-DTPA-BMA for cancer therapy. The aim of this study was to develop and validate a chemometric-assisted method by hydrophilic interaction liquid chromatography (HILIC) for determination of Gd-DTPA-BMA in liposomes. The chromatographic conditions obtained were: Sequant® ZIC®-HILIC Merck (150 × 4.6 mm, 3.5 µm, 100 A) column, mobile phase composed of 5 mmol L-1 ACN/NH4FA, pH 4.5 (60:40 v/v) at 0.6 mL min-1, injection volume of 20 µL, temperature of 30 oC, and detection at 210 nm. The linear range was of 40 to 120 nmol mL-1. The use of chemometrics allowed obtaining optimal chromatographic parameters, in terms of signal-to-noise ratio, resolution, and asymmetry.

Despite advances in the development of new therapeutic agents and diagnostic imaging techniques, the 5-year survival of osteosarcoma, the most common type of bone cancer, remains practically unaltered for the last three decades at around 60%. Nanoparticle-based carriers have emerged as new class of drug delivery systems that could potentially overcome conventional chemotherapy limitations, by promoting a better drug biodistribution profile by allowing a preferential accumulation of the drug in the desired tissue, while minimising non-targeted tissue toxicity, thus resulting in an improved overall therapeutic effectiveness. Hydroxyapatite nanoparticles (HANP) are known to be biocompatible and non-immunogenic and have shown to be preferentially accumulated in bone tissues being considered a promising carrier to bone tissues. Herein, we successfully synthesised mesoporous hydroxyapatite nanoparticles with mean size of 285.32 ± 10.29 nm and superficial area of 103.5 m2/g, containing significant quanti...

Despite recent advances in the development of new therapeutic agents and diagnostic imaging modalities, cancer is still one of the main causes of death worldwide. A better understanding of the molecular signature of cancer has promoted the development of a new generation of anti-cancer drugs and diagnostic agents that specifically target molecular components such as genes, ligands, receptors and signaling pathways. However, intrinsic heterogeneity of tumors has hampered the overall success of target therapies even among patients with similar tumor types but unpredictable different responses to therapy. In this sense, post-treatment response monitoring becomes indispensable and nuclear medicine imaging modalities could provide the tools for an early indication of therapeutic efficacy. Herein, we briefly discuss the current role of PET and SPECT imaging in monitoring cancer therapy together with an update on the current radiolabeled probes that are currently investigated for tumor therapy response assessment.

The knowledge transmission in scientific education demands the formulation of methods capable to insert between student and the study object a nearness, making the student apt to build, from autodidactic posture, solutions that only the professional formation can produce. In this sense, a teaching should develop an effective pedagogy, focusing on knowledge production and its preservation, helping the scientific progress. Guided by these concepts, the educational process can be considered complex and should focus on the quality of the transmitted knowledge, through strategies that ensure the maximum information accessibility. In strictu sensu post-graduation context, some particularities related to the knowledge building and not so only the concepts memorization should have more attention, due to the scientific and teacher training goals. The medicinal chemistry area exhibits the necessity to have a great interlocution with other chemistry disciplines, such as organic chemistry, analytical chemistry and as well as disciplines related to human health. In this sense, the evaluation of learning process becomes, currently, a great challenge for professors that seek to develop the interdisciplinary sense. Considering this reality, in this study, the authors present a classroom experience, where specific competences developed in students of medicinal chemistry discipline was a target of evaluation based on creation of review text. From the results obtained was possible to rethink strategies that can contribute to foster new forms to evaluate the learning process based on competences development.

Today, cancer represents one of the main causes of death worldwide, making it a formidable challenge for all scientific areas that seek new therapeutic approaches for its cure. As a therapeutic approach, radiotherapy, widely used in treating various types of tumors, acts by not discriminating healthy cells from tumor cells. Seeking to minimize these effects, nanostructured carriers of radioisotopes have been studied with the aim of improving the specificity of action of ionizing radiation, delivering and retaining adequate amounts of radioactive isotopes within tumor cells, leading them to death. In the present work, silica nanoparticles were prepared in order to evaluate their capacity to act as a nanocarrier of the 159Gd-DTPA-BMA radioactive complex, which can selectively deliver high radiation doses to tumors. Furthermore, this formulation seeks to prevent nontarget tissues from receiving excessive amounts of radiation, acting as a new potential alternative to conventional radiotherapy, in which a larg...

In the present work, mesoporous silica SBA-16 nanoparticles with an innovative cubic mesoporous matrix, practically unexplored in terms of functionalization and in vitro studies, has been synthesized and functionalized using two different silanizing agents: 3-amino-propyl-triethoxysilane (APTES) and n-propyltriethoxysilane (PTES). The pure and functionalized silica nanoparticles were physicochemically and morphologically characterized, the results of which presented adequate characteristics for in vitro and in vivo applications. The influence of the functionalization process on the incorporation rate and kinetic release of a model drug (Atenolol) was also studied. These results revealed that samples functionalized with APTES presented a negligible release of Atenolol from the nanoparticles in simulated body fluid (SBF). This is an important result when seeking to avoid the premature release of chemotherapeutic agents or radioisotopes into the bloodstream until it reaches its final destination. Finally, the cytocompatibility in vitro tests were conducted in an MRC-5 cell line, human fetal lung fibroblast cells, at different concentrations. The results indicated no significant change in cell morphology, chromosomal changes, or increase of ROS in the MRC-5 cells related to the control group. All findings from this study reveal a potential application of mesoporous silica SBA-16 nanoparticles as new potential drugs or radioisotope nanocarriers to be applied in therapeutic or diagnostic procedures.

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon over-express receptors for bombesin-like peptides. Therefore, radiolabeled bombesin analogs might be useful for tumor identification. Nevertheless, it is well known that higher tumor uptake can yield images in higher quality. Hence, drug delivery systems, such as liposomes, can be used to achieve a higher concentration of radiotracer in tumor site, and also improve the radiotracer stability, since peptides can suffer easily degradation in vivo by natural plasma and tissue peptides. In this paper, we prepared long-circulating, pH-sensitive liposomes and long-circulation, non-pH sensitive liposomes. Both formulations were able to encapsulate the radiolabeled bombesin derivative (99mTc-BBN(7_14)), and also showing high in vitro stability. Biodistribution studies were performed in Ehrlich tumor bearing-mice to compare the ability of pH-sensitive and non-pH sensitive liposomes to deliver 99mTc-BBN(7_14) to tumor site. Results showed higher tumor uptake (2-fold) when pH-sensitive liposomes were used, suggesting that these vesicles can facilitate the access to the tumor by releasing the diagnostic agent into the ideal area. As a result, tumor-to-muscle ratio achieved with pH-sensitive liposomes was higher than that obtained with non-pH-sensitive formulation. In addition, scintigraphic images for pH-sensitive liposomes showed evident tumor uptake, corroborating with biodistribution data. Therefore, the results presented in this paper suggest that pH-sensitive liposomes are able to deliver more efficiently the radiolabeled bombesin analog. This finding poses a new possibility to improve images quality, since the tumor-to-muscle ratio was strongly enhanced.

The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery.

The aim of this study was develop, characterize and assess the cytotoxic activity of pH-sensitive (pHL-Gd), stealth pH-sensitive (SpHL-Gd), and conventional (convL-Gd) liposomes containing gadodiamide (Gd-DTPA-BMA). Formulations were prepared by reverse-phase evaporation method and their physicochemical properties were evaluated by means of particle size, zeta potential, and Gd-DTPA- BMA entrapment. SpHL-Gd was considered the most promising liposome, since it combines stealth and fusogenic characteristics that can contribute for higher therapeutic efficiency. Their encapsulation efficiency has been optimized satisfactorily. The addition of Gd-DTPA- BMA at 125 µmol/mL in the SpHL-Gd preparation allowed obtaining liposomes with appropriate encapsulation efficiency (20.3 ˜ 0.1%) and entrapment (25.4 ˜ 0.1 µmol/mL), reducing the expense of drugs employed in the process. The cytotoxic studies on the 4T1 breast cancer cell line demonstrated that Gd-DTPA- BMA loaded in liposomes significantly inhibited cancer cell viability. pHL-Gd and SpHL-Gd liposomes showed higher activity than convL-Gd and free Gd-DTPA- BMA, indicating that the pH-sensitive characteristic was important to improve intracellular delivery. Moreover, the presence of polyethylene glycol (PEG) in the SpHL-Gd formulation did not affected the pH-sensitivity and internalization. Therefore, the results of this study suggest the applicability of liposomes containing Gd-DTPA- BMA as a new promising controlled delivery system.

Summary Forest hydrology has been widely investigated, but the impacts of different woodland types on hydrological processes within a peri-urban catchment mosaic are poorly understood. This paper investigates overland flow generation processes in three different types of woodland in a small (6.2 km2) catchment in central Portugal that has undergone strong urban development over the past 50 years. A semi-natural oak stand and a sparse eucalyptus stand on partly abandoned peri-urban land and a dense eucalyptus plantation were each instrumented with three 16 m2 runoff plots and 15 throughfall gauges, which were monitored at c. 1- to 2-week intervals over two hydrological years. In addition, surface soil moisture content (0–5 cm) and hydrophobicity (0–2 cm, 2–5 cm and 5–7 cm) were measured at the same time as overland flow and throughfall. Although all three woodland types produced relatively little overland flow (

In this work the apoptosis mediated by caspase-3 and p53-dependent anticancer effects of 159Gd-DTPA-BMA metal complex were evaluated against RT2 glioblastoma cells. The results showed that the mechanism of cell death involves apoptosis by caspase-3 activation. Furthermore, the involvement of p53 protein triggered by 159Gd-DTPA-BMA in these cells was verified preliminarily. Considering these finding, the radioactive complex can be considered as potential therapeutic alternative agent against cancer.

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 99mTc 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.

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the 159Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer.

The metaiodobenzylguanidine (MIBG) radiopharmaceutical, an analogue of norepinephrine, has been used to diagnose certain diseases in the cardiovascular system when radiolabeled with 123I. This radiopharmaceutical can also be used to treat tumors, such as neuroblastomas and pheochromocytomas, when radiolabeled with 131I. Its clinical use is often accompanied by a slow intravenous administration, where a significant dose of radiation can directly affect workers in nuclear medicine services. To overcome this problem, the incorporation and controlled release of radiopharmaceuticals from the matrix of mesoporous systems based on silica, such as SBA-15 and hybrid [SBA-15/P(N-iPAAm)], can lead to a significant reduction in radiation doses received by workers. In the present study, silica matrices SBA-15 and hybrid [SBA-15/P(N-iPAAm)] containing the radiopharmaceutical MIBG were prepared and physicochemically characterized through FTIR, SEM, and small angle X-ray diffraction techniques. The release profiles of MIBG from SBA-15 and [SBA-15/P(N-iPAAm)] were studied in a simulated body fluid (SBF) to evaluate their potential application as vehicles for controlled releases. Furthermore, in vitro studies were performed to assess the cytotoxicity of matrices as compared to human lung fibroblast cells (MRC-5). The results revealed that the amount of MIBG incorporated within the studied matrices was indeed quite different, showing that only the hybrid [SBA-15/P(N-iPAAm)] system allowed for a more adequate release profile of MIGB. Taking all results into consideration, it can be concluded that the hybrid matrix [SBA-15/P(N-iPAAm)] can be considered a potential alternative material for the controlled release delivery of radio-pharmaceuticals.

PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the Gd-DTPA-BMA complex were prepared and radiolabeled by neutron activation. The radiolabeled liposomes presented significant in vitro cytotoxic activity against Ehrlich tumor cells when compared with controls. The biodistribution profile of these liposomes and free (159)Gd-DTPA-BMA were studied in mice bearing a previously-developed solid Ehrlich tumor. The results demonstrated an important uptake of the formulations by the tumor tissue, with a tissue/blood partition coefficient (Kp) 3.88 and 14.16 times higher than that of the free complex for pH-sensitive PEG-coated and PEG-folate-coated liposomes containing the (159)Gd-DTPA-BMA complex, respectively. Both formulations accumulated in the liver and spleen, thereby revealing some difficulty in escaping the action of the MPS cells. The formulation without folate presented a lower renal uptake, which is desirable in patients with chronic renal failure due to the potential risk of nephrogenic systemic fibrosis (NFS). The scintigraphic study revealed that the target/non-target ratio is always greater than three for pH-sensitive PEG-coated liposome formulations and above nine for pH-sensitive PEG-folate-coated liposome formulations. The results obtained in this study demonstrated that the formulations employed can be considered to be a potential alternative for the treatment of cancer, including patients with chronic renal failure.

The present work describes the preparation, labeling, physicochemical characterization, and in vitro cytotoxic evaluation of long circulating pH-sensitive liposomes containing 159Gd-DTPA-BMA. These liposomes were successfully obtained and submitted to neutron irradiation for gadolinium labeling. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy, while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by atomic force microscopy. The stability and release profiles of Gd-DTPA-BMA in the liposomes were determined in vitro in Dubelco's Modified Eagle's Medium and rat serum at 70%. The results showed that liposomes remained physically stable after 8 h of irradiation and presented a low release profile of its content in two different biological mediums. The formulation of liposomes containing 159Gd and its respective controls were evaluated by in vitro cytotoxicity against tumor cells RT2. The results showed increased cytotoxic activity of approximately 1170 fold in relation to free Gd-DTPA-BMA.

Beta emitting radionuclides, such as 90Y, 153Sm, and 131I, with short half lives and that deliver a higher radiation dose rate, have been used effectively in alleviating bone pain due to metastases, synovectomy, and tumor therapy. The 159Gd is a radionuclide that presents these characteristics; however, its antitumoral potential has yet to be investigated. The present study aims to identify the 159Gd production, structural characterization, and antitumoral activity. To achieve these objectives, Gadodiamide®, the most non-ionic dye used in nuclear magnetic resonance imaging, was neutron irradiated for 8 h to obtain 159Gd-Gadodiamide. A final product with high specific activity was obtained, and its structural integrity was determined by Fourier Transformer Infrared Spectroscopy and High Performance Liquid Chromatography methods. Finally, the irradiated product presented good stability and increased to approximately 95 times that of the in vitro cytotoxicity of the gadodiamide against Ehrlich tumor cells. These results suggest that there is a high potential for the use of 159Gd against tumoral cells.

Soil erosion is a serious environmental problem. An estimation of the expected soil loss by water-caused erosion can be calculated considering the Revised Universal Soil Loss Equation (RUSLE). Geographical Information Systems (GIS) provide different tools to create categorical maps of soil erosion risk which help to study the risk assessment of soil loss. The objective of this study was to develop a GIS open source application (in QGIS), using the RUSLE methodology for estimating erosion rate at the watershed scale (desktop application) and provide the same application via web access (web application). The applications developed allow one to generate all the maps necessary to evaluate the soil erosion risk. Several libraries and algorithms from SEXTANTE were used to develop these applications. These applications were tested in Montalegre municipality (Portugal). The maps involved in RUSLE method-soil erosivity factor, soil erodibility factor, topographic factor, cover management factor, and support practices-were created. The estimated mean value of the soil loss obtained was 220 ton km(-2) year(-1) ranged from 0.27 to 1283 ton km(-2) year(-1). The results indicated that most of the study area (80 %) is characterized by very low soil erosion level (321 ton km(-2) year(-1)) and in 4 % of the studied area the soil erosion was higher than 962 ton km(-2) year(-1). It was also concluded that areas with high slope values and bare soil are related with high level of erosion and the higher the P and C values, the higher the soil erosion percentage. The RUSLE web and the desktop application are freely available.

Long-circulating and pH-sensitive liposomes trapping 99m Tc-HYNIC-βAla-bombesin (7–14) (aSpHL- 99m Tc-BBN (7–14) ) were successfully prepared. Biodistribution studies and scintigraphic images were performed in Ehrlich tumor-bearing Swiss mice. This system showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Therefore, aSpHL- 99m Tc-BBN (7–14) could be considered as a potential agent for tumor diagnosis.