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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.

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.

Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri–liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri–liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri–liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential.

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...

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.

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.

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.

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.

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...

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.