Grupo: Bionanopartículas Metálicas (BioNanomet) (FQM368)
https://hdl.handle.net/10481/47204
2024-03-29T10:21:51ZMagneto-optical hyperthermia agents based on probiotic bacteria loaded with magnetic and gold nanoparticles
https://hdl.handle.net/10481/73672
Magneto-optical hyperthermia agents based on probiotic bacteria loaded with magnetic and gold nanoparticles
Garcés Robles, Víctor Jesús; González, Ana; Gálvez Rodríguez, Natividad; Delgado López, José Manuel; Calvino Gámez, José Juan; Trasobares Llorente, Susana; Fernández-Afonso, Yllian; Gutiérrez, Lucia; Domínguez Vera, José Manuel
Probiotic bacteria were used as carriers of metallic nanoparticles to develop innovative oral agents for hyperthermia cancer therapy. Two synthetic strategies were used to produce the different therapeutic agents. First, the probiotic bacterium Lactobacillus fermentum was simultaneously loaded with magnetic (MNPs) and gold nanoparticles (AuNPs) of different morphologies to produce AuNP+MNP-bacteria systems with both types of nanoparticles arranged in the same layer of bacterial exopolysaccharides (EPS). In the second approach, the probiotic was first loaded with AuNP to form AuNP-bacteria and subsequently loaded with MNP-EPS to yield AuNP-bacteria-EPS-MNP with the MNP and AuNP arranged in two different EPS layers. This second strategy has never been reported and exploits the presence of EPS–EPS recognition which allows the layer-by-layer formation of structures on the bacteria external wall. The AuNP+MNP-bacteria and AuNP-bacteria-EPS-MNP samples were characterized by scanning (SEM) and transmission electron microscopy (TEM), and UV-vis spectroscopy. The potential of these two heterobimetallic systems as magnetic hyperthermia or photothermal therapy agents was assessed, validating their capacity to produce heat either during exposure to an alternating magnetic field or a near-infrared laser light. The probiotic Lactobacillus fermentum has already been proposed as an oral drug carrier, able to overcome the stomach medium and deliver drugs to the intestines, and it is actually marketed as an oral supplement to reinforce the gut microbiota, thus, our results open the way for the development of novel therapeutic strategies using these new heterobimetallic AuNP/MNP-bacteria systems in the frame of gastric diseases, using them, for example, as oral agents for cancer treatment with magnetic hyperthermia and photothermal therapy.
This work was funded by the Ministerio de Ciencia, Innovación
y Universidades (MCIU), the Agencia Estatal de Investigación
(AEI) and Fondo Europeo de Desarrollo Regional (FEDER)
through the projects PID2019- 111461GB-I00 to N.G. and
J.M.DV, and PGC2018-096016-B-I00 to LG.). S.T. and J.J.C.
acknowledge funding from the European Union’s Horizon 2020
research and innovation program under Grant
823717−ESTEEM3. A.G. acknowledges Junta de Andalucía for
the postdoctoral contract within the PAIDI 2020 program
(DOC_00791). Y.FA. thanks Santander-Universidad Zaragoza
Fellowship program for her PhD position. J.M.D.L.
acknowledges the financial support by the Spanish MCIN/AEI
/10.13039/501100011033 through the project
NanoSmart (RYC-2016-21042)
Optical and tomography studies of water-soluble gold nanoparticles on bacterial exopolysaccharides
https://hdl.handle.net/10481/72299
Optical and tomography studies of water-soluble gold nanoparticles on bacterial exopolysaccharides
González, Ana; Garcés, Víctor; Sabio Rodríguez, Laura; Velando, Félix; López Haro, Miguel; Gálvez Rodríguez, Natividad; Calvino, José J; Domínguez-Vera, Jose M.
Gold nanoparticles of different shapes (spherical, rods, and prisms) aggregate when deposited onto Lactobacillus fermentum's exopolysaccharide (EPS), a set of polysaccharides excreted by the bacteria. Transmission electron microscopy studies revealed that gold nanoparticles have high affinity for EPS. UV-vis spectra of aggregated gold nanoparticles showed additional absorbance peaks at lower energies in comparison with isolated nanoparticles. In the case of gold nanoprisms, the aggregation leads to a new absorption at a very low energy centered at 1100 nm. Moreover, the EPS of L. fermentum itself produces gold aggregates from a Au(III) solution. Surface-enhanced Raman spectroscopy performances for the detection of rhodamine B of gold aggregates were drastically different. A tomography study on all samples revealed clear differences in the extension of the EPS coating on the gold nanoparticles. Only the gold aggregate in which gold interparticle surfaces were exposed to RhB showed a drastic increase (two orders of magnitude) of intensity in the Raman spectrum of RhB
This work was funded by MINECO and FEDER (Project
Nos. CTQ2015-64538-R and MAT2013-40823-R). Junta de
Andalucia (Nos. FQM368 and FQM334) is also acknowledged.
M. López-Haro acknowledges funding from Juan de la Cierva
MINECO Program (Ref. No. IJCI-2014-19367). ET experiments
were run at the Electron Microscopy Division (DME) of
SC-ICYT UCA.
Varying iron release from transferrin and lactoferrin proteins. A laboratory experiment
https://hdl.handle.net/10481/54125
Varying iron release from transferrin and lactoferrin proteins. A laboratory experiment
Carmona, Fernando; González, Ana; Sánchez, Manu; Gálvez Rodríguez, Natividad; Cuesta, Rafael; Capdevila, Mercè; Domínguez-Vera, Jose M.
Iron metabolism is an important subject of study for undergraduate students of chemistry and biochemistry. Relevant laboratory exercises are scarce in the literature but would be very helpful in assisting students grasp key concepts. The experiment described here deals with different iron release mechanisms of two protagonists in iron metabolism: serum transferrin (Tf) and lactoferrin (Lf). Despite having very similar structures and iron‐binding sites, Tf releases practically all its iron at pH 5.5 while Lf requires a significantly lower pH of 3. This difference in behavior is directly related to their respective biological functions as Tf blood‐borne iron into the cell, while Lf competes with pathogens to sequester iron in biological fluids at more acidic pHs.
During this experiment, the students will carry out iron loading and unloading on both human Lf and Tf and monitor the iron release at different pHs using UV–Vis spectroscopy. With this simple approach, the students will discover the different patterns of iron release of Tf and Lf and how this variance in behavior relates to their biological functions. Furthermore, this laboratory practice can be expanded to allow students to investigate a variety of iron proteins.
Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption
https://hdl.handle.net/10481/54124
Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption
González, Ana; Gálvez Rodríguez, Natividad; Martín, Jesús; Reyes, Fernando; Pérez-Victoria, Ignacio; Domínguez-Vera, Jose M.
We have taken a vital step towards understanding why probiotic bacteria increase iron absorption in the gastrointestinal tract. We show here that Lactobacillus fermentum, one of the main probiotics of the microbiota, exhibits an extraordinary ferric-reducing activity. This activity is predominantly due to an excreted molecule: p-hydroxyphenyllactic acid (HPLA). Reduction of Fe(III) to Fe(II) is essential for iron absorption in the gastrointestinal tract. By reducing Fe(III), HPLA boosts Fe(II) absorption through the DMT1 channels of enterocytes. An in vitro experiment tested and confirmed this hypothesis. This discovery opens new avenues for the treatment of iron deficiency in humans, one of the most common and widespread nutritional disorders in the world.
Bacteria-Carried Iron Oxide Nanoparticles for Treatment of Anemia
https://hdl.handle.net/10481/54123
Bacteria-Carried Iron Oxide Nanoparticles for Treatment of Anemia; Bacteria-Carried Iron Oxide Nanoparticles for Treatment of Anemia
Garcés, Víctor; Rodríguez Nogales, Alba; González, Ana; Gálvez Rodríguez, Natividad; Rodríguez Cabezas, María Elena; García-Martín, Maria L.; Gutiérrez, Lucia; Rondón, Deyanira; Olivares Martín, Mónica; Gálvez, Julio; Domínguez-Vera, Jose M.
The efficiency of maghemite nanoparticles for the treatment of anemia was sensibly higher when nanoparticles were incorporated onto the probiotic bacterium Lactobacillus fermentum (MNP-bacteria) than when administrated as uncoated nanoparticles (MNP). Plasma iron and hemoglobin, intestine expression of divalent metal transporter 1 (DMT1) and duodenal Cytochrome b (DcytB), as well as hepatic expression of the hormone hepcidin were fully restored to healthy levels after administration of MNP-bacteria but not of MNP. A magnetic study on biodistribution and biodegradation showed accumulation of maghemite nanoparticles in intestine lumen when MNP-bacteria were administrated. In contrast, MNP barely reached intestine. In vivo MRI studies suggested the internalization of MNP-bacteria into enterocytes, which did not occur with MNP. Transmission electronic microscopy confirmed this internalization. The collective analysis of results point out that L. fermentum is an excellent carrier to overcome the stomach medium and drive maghemite nanoparticles to intestine, where iron absorption occurs. Due the probiotic ability to adhere to the gut wall, MNP-bacteria internalize into the enterocyte, where maghemite nanoparticles are delivered, providing an adequate iron level into enterocyte. This paper advances a new route for effective iron absorption in the treatment of anemia.; The efficiency of maghemite nanoparticles for the treatment of anemia was sensibly higher when nanoparticles were incorporated onto the probiotic bacterium Lactobacillus fermentum (MNP-bacteria) than when administrated as uncoated nanoparticles (MNP). Plasma iron and hemoglobin, intestine expression of divalent metal transporter 1 (DMT1) and duodenal Cytochrome b (DcytB), as well as hepatic expression of the hormone hepcidin were fully restored to healthy levels after administration of MNP-bacteria but not of MNP. A magnetic study on biodistribution and biodegradation showed accumulation of maghemite nanoparticles in intestine lumen when MNP-bacteria were administrated. In contrast, MNP barely reached intestine. In vivo MRI studies suggested the internalization of MNP-bacteria into enterocytes, which did not occur with MNP. Transmission electronic microscopy confirmed this internalization. The collective analysis of results point out that L. fermentum is an excellent carrier to overcome the stomach medium and drive maghemite nanoparticles to intestine, where iron absorption occurs. Due the probiotic ability to adhere to the gut wall, MNP-bacteria internalize into the enterocyte, where maghemite nanoparticles are delivered, providing an adequate iron level into enterocyte. This paper advances a new route for effective iron absorption in the treatment of anemia.