Iron Oxide Nanoparticles in Photothermal Therapy

Photothermal therapy is a kind of therapy based on increasing the temperature of tumoral cells above 42 C. To this aim, cells must be illuminated with a laser, and the energy of the radiation is transformed in heat. Usually, the employed radiation belongs to the near-infrared radiation range. At this range, the absorption and scattering of the radiation by the body is minimal. Thus, tissues are almost transparent. To improve the efficacy and selectivity of the energy-to-heat transduction, a light-absorbing material, the photothermal agent, must be introduced into the tumor. At present, a vast array of compounds are available as photothermal agents. Among the substances used as photothermal agents, gold-based compounds are one of the most employed. However, the undefined toxicity of this metal hinders their clinical investigations in the long run. Magnetic nanoparticles are a good alternative for use as a photothermal agent in the treatment of tumors. Such nanoparticles, especially those formed by iron oxides, can be used in combination with other substances or used themselves as photothermal agents. The combination of magnetic nanoparticles with other photothermal agents adds more capabilities to the therapeutic system: the nanoparticles can be directed magnetically to the site of interest (the tumor) and their distribution in tumors and other organs can be imaged. When used alone, magnetic nanoparticles present, in theory, an important limitation: their molar absorption coefficient in the near infrared region is low. The controlled clustering of the nanoparticles can solve this drawback. In such conditions, the absorption of the indicated radiation is higher and the conversion of energy in heat is more efficient than in individual nanoparticles. On the other hand, it can be designed as a therapeutic system, in which the heat generated by magnetic nanoparticles after irradiation with infrared light can release a drug attached to the nanoparticles in a controlled manner. This form of targeted drug delivery seems to be a promising tool of chemo-phototherapy. Finally, the heating efficiency of iron oxide nanoparticles can be increased if the infrared radiation is combined with an alternating magnetic field

Prussian Blue: A Safe Pigment with Zeolitic-Like Activity

Prussian blue (PB) and PB analogues (PBA) are coordination network materials that present important similarities with zeolites concretely with their ability of adsorbing cations. Depending on the conditions of preparation, which is cheap and easy, PB can be classified into soluble PB and insoluble PB. The zeolitic-like properties are mainly inherent to insoluble form. This form presents some defects in its cubic lattice resulting in an open structure. The vacancies make PB capable of taking up and trapping ions or molecules into the lattice. Important adsorption characteristics of PB are a high specific area (370 m2 g−1 determined according the BET theory), uniform pore diameter, and large pore width. PB has numerous applications in many scientific and technological fields. PB are assembled into nanoparticles that, due to their biosafety and biocompatibility, can be used for biomedical applications. PB and PBA have been shown to be excellent sorbents of radioactive cesium and radioactive and nonradioactive thallium. Other cations adsorbed by PB are K+, Na+,NH4+, and some divalent cations. PB can also capture gaseous molecules, hydrocarbons, and even luminescent molecules such as 2-aminoanthracene. As the main adsorptive application of PB is the selective removal of cations from the environment, it is important to easily separate the sorbent of the purified solution. To facilitate this, PB is encapsulated into a polymer or coats a support, sometimes magnetic particles. Finally, is remarkable to point out that PB can be recycled and the adsorbed material can be recovered

Magnetic nanoparticles: From diagnosis to therapy

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/128014Magnetic nanoparticles have proven to be promising theranostic agents, namely tools for therapy and diagnosis. Among them, superparamagnetic iron oxide nanoparticles (SPIONs) highlight for their biocompatibility and reduced toxicity. Here, we describe the synthesis and characterization of SPIONs by co-precipitation of ferric and ferrous salts under mild conditions. These particles were able to accumulate in inflamed areas fact that was increased upon the application of an external magnetic field. Resonance magnetic imaging studies have shown their suitability as negative contrast agents for diagnosis. In addition, hybrid nanoparticles were obtained by incorporating the above described SPIONs into liposomes or nanoemulsions. The findings have confirmed the high potential of these systems for biomedical applications

Mediators of cachexia in cancer patients

Alterations in amino acid and protein metabolism particularly in skeletal muscle are a key feature of cancer that contributes to the cachexia syndrome. Thus, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. These changes are promoted by both hormonal alterations and inflammatory mediators released as a result of the systemic inflammatory response induced by the tumor. Other events, such as alterations in the rate of myogenesis/apoptosis and decreased regeneration potential also affect skeletal muscle in patients with cancer. Mitochondrial dysfunction also contributes to changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators either released by the tumor or by the patient's healthy cells are responsible for the activation of these catabolic processes that take place in skeletal muscle and in other tissues/organs, such as liver or adipose tissues. Indeed, white adipose tissue is also subject to extensive wasting and 'browning' of some of the white adipocytes into beige cells; therefore increasing the energetic inefficiency of the patient with cancer. Recently, an interest in the role of micromRNAs either free or transported into exosomes has been related to the events that take place in white adipose tissue during cancer cachexia

Production of bacterial oxylipins by Pseudomonas aeruginosa 42A2

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/67430Oxylipins are a family of natural compounds that are reported to perform a variety of biological functions. Besides the biological properties of such compounds, interest in hydroxy fatty acids is increasing, due to the industrial applications of these renewable compounds as a starting material for resins, emulsifiers, plastics or polyesters. Hydroxy fatty acids are used as thickeners in a new generation of emulsifiers and lubricants, to reach new levels of performance. When grown in submerged culture with oleic or linoleic acid, Pseudomonas aeruginosa 42A2 produced several oxylipins. In this study, oxylipin production and its applications are examined

Magnetic nanoemulsions: comparison between nanoemulsions formed by ultrasonication and by spontaneous emulsification

Nanoemulsions are particularly suitable as a platform in the development of delivery systems. The type of nanoemulsion with a higher stability will offer an advantage in the preparation of a delivery system for lipophilic drugs. Nanoemulsions can be fabricated by different processing methods, which are usually categorized as either high- or low-energy methods. In this study, a comparison between two methods of preparing magnetic oil-in-water (O/W) nanoemulsions is described. The nanoemulsions were formed by sonication (the high-energy method) or by spontaneous emulsification (the low-energy method). In both cases, the oil phase was olive oil, and a phospholipid and a pegylated phospholipid were used as emulsifiers. To favor the comparison, the amounts of the components were the same in both kinds of nanoemulsions. Moreover, nanoemulsions were loaded with hydrophobic superparamagnetic nanoparticles and indomethacin. In vitro, releases studies indicated a short drug burst period followed by a prolonged phase of dissolutive drug release. The Korsmeyer-Peppas model can fit the associated kinetics. The results showed that such nanoemulsions are suitable as a platform in the development of delivering systems for lipophilic drugs. The long-term stability was also examined at different temperatures, as well as the interaction with plasma proteins. Nanoemulsion obtained by the low-energy method showed a great stability at 4 C and at ambient temperature. Its size and polydispersity did not change over more than two months. The spontaneous emulsification method therefore has great potential for forming nanoemulsion-based delivery systems

Immunoliposome-mediated drug delivery to Plasmodium-infected and non-infected red blood cells as a dual therapeutic/prophylactic antimalarial stragegy

One of the most important factors behind resistance evolution in malaria is the failure to deliver sufficiently high amounts of drugs to early stages of Plasmodium-infected red blood cells (pRBCs). Despite having been considered for decades as a promising approach, the delivery of antimalarials encapsulated in immunoliposomes targeted to pRBCs has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here we show that encapsulation efficiencies reaching N96% are achieved for the weak basic drugs chloroquine (CQ) and primaquine using the pH gradient loading method in liposomes containing neutral saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the delivery to the cell of drugs not affecting the erythrocytic metabolism. Using this strategy, we have achieved unprecedented complete nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Immunoliposomes studded with monoclonal antibodies raised against the erythrocyte surface protein glycophorin A were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with N95% of added liposomes retained on cell surfaces. When exposed for only 15 min to Plasmodium falciparum in vitro cultures of early stages, free CQ had no significant effect on the viability of the parasite up to 200 nM, whereas immunoliposomal 50 nM CQ completely arrested its growth. In vivo assays in mice showed that immunoliposomes cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg, whereas free CQ administered at 1.75 mg/kgwas, atmost, 40-fold less efficient. Our data suggest that this significant improvement is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion

Dual responsive gelatin-based nanoparticles for enhanced 5-fluorouracil efficiency

The very slow progress in the therapeutic efficacy of the treatment of severe diseases has suggested the use of a growing need for a multidisciplinary approach to the delivery of therapeutics to targets tissues. There has been increasing effort in the design of stimuli-responsive nanomaterials that they will be developed into effective drug delivery vehicles. Most commonly, effective drug delivery is associated with nanomaterial-facilitated accumulation and/or cellular internalization. Recent studies in our lab have demonstrated that gelatin-based NPs can be considered suitable pH responsive devices for the effective intracellular delivery of drugs. Concerning cancer treatment, ligands recognizing tumour-associated antigens expressed on the surface of the tumour cells have been employed. Some of the target structures suitable for tumour targeting belong to integrins which mediate cell adhesion to extracellular matrix and other cells. Interestingly, gelatin chains contain motifs such as RGD sequences that can be recognised by integrins. In this work the inclusion of the anticancer drug 5-fluorouracil (5-FU) on these gelatin-based NPs has been projected. These NPs may provide an opportunity to increase the therapeutic effect using a dual approach by: i) targeting the therapeutic drug to the tumour cells by the action of the naturally occurring RGD-motif on gelatin and ii) minimizing the non-productive trafficking from endosomes to lysosomes by releasing the cargo using the charge reversal approach after cellular internalization. In vitro cytotoxicity experiments of NPs on tumoral and non-tumoral cell lines have reported selectivity indexes higher than 30 demonstrating a great selectivity on the mode of action as a function of the cell line and the imposed compositions. Keywords: 5-fluorouracil; Gelatin; In vitro cytotoxicity; Loading efficiency; Nanoparticles; Selectivity. Copyright © 2018 Elsevier B.V. All rights reserved

Physicochemical characterization of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide: Interaction with model membranes

Four peptide sequences corresponding to the E1 protein of GBV-C: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10) and QAGLAVRPGKSAAQLVGE (P18) were studied as they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP). In this work, the surface properties of the E1 peptide sequences are investigated and their physicochemical characterization is done by studying their interaction with model membranes; moreover, their mixtures with HIV-1 FP were also studied in order to observe whether they are capable to modify the HIV-1 FP interaction with model membranes as liposomes or monolayers. Physicochemical properties of peptides (pI and net charge) were predicted showing similarities between P7 and P8, and P10 and HIV-1 FP, whereas P18 appears to be very different from the rest. Circular dichroism experiments were carried out showing an increase of the percentage of α-helix of P7 and P8 when mixed with HIV-1 FP corroborating a conformational change that could be the cause of their inhibition ability. Penetration experiments show that all the peptides can spontaneously insert into phospholipid membranes. Analysis of compression isotherms indicates that the peptides interact with phospholipids and the E1 peptides modify the compression isotherms of HIV-1 FP, but there is one of the peptides that excelled as the best candidate for inhibiting the activity of HIV-1 FP, P7, and therefore, that could be potentially used in future anti-HIV-1 research