18 research outputs found
Tuning properties of biomimetic magnetic nanoparticles by combining magnetosome associated proteins
The role of magnetosome associated proteins on the in vitro synthesis of magnetite nanoparticles has
gained interest, both to obtain a better understanding of the magnetosome biomineralization process
and to be able to produce novel magnetosome-like biomimetic nanoparticles. Up to now, only one
recombinant protein has been used at the time to in vitro form biomimetic magnetite precipitates,
being that a scenario far enough from what probably occurs in the magnetosome. In the present study,
both Mms6 and MamC from Magnetococcus marinus MC-1 have been used to in vitro form biomimetic
magnetites. Our results show that MamC and Mms6 have different, but complementary, effects on in
vitro magnetite nucleation and growth. MamC seems to control the kinetics of magnetite nucleation
while Mms6 seems to preferably control the kinetics for crystal growth. Our results from the present
study also indicate that it is possible to combine both proteins to tune the properties of the resulting
biomimetic magnetites. In particular, by changing the relative ratio of these proteins, better faceted
and/or larger magnetite crystals with, consequently, different magnetic moment per particle could be
obtained. This study provides with tools to obtain new biomimetic nanoparticles with a potential utility
for biotechnological applicationsWe acknowledge projects CGL2013-46612 and CGL2016-76723 from the Ministerio de Economía y
Competitividad from SPAIN and Fondo Europeo de Desarrollo Regional (FEDER) for financial support and
Unidad Científica de Excelencia UCE-PP2016-05 of the University of Granada. Thanks go to CIC personnel
of the University of Granada for technical assistance in the CD, TEM, SQUID and Unidad de Radioquímica e Inmunoanalisis (LAR), to the Proteomics Unit personnel of the Institute of Parasitology and Biomedicine “López-
Neyra” (IPBLN) for technical assistance in the PMF and PFF by MALDI-TOF/TOF, and to the University of
Málaga for technical assintance in HRTEM measurements
Enhancement of Magnetic Hyperthermia by Mixing Synthetic Inorganic and Biomimetic Magnetic Nanoparticles
In this work we report on the synthesis and characterization of magnetic nanoparticles of
two distinct origins, one inorganic (MNPs) and the other biomimetic (BMNPs), the latter based on a
process of bacterial synthesis. Each of these two kinds of particles has its own advantages when used
separately with biomedical purposes. Thus, BMNPs present an isoelectric point below neutrality
(around pH 4.4), while MNPs show a zero-zeta potential at pH 7, and appear to be excellent agents for
magnetic hyperthermia. This means that the biomimetic particles are better suited to be loaded with
drug molecules positively charged at neutral pH (notably, doxorubicin, for instance) and releasing it
at the acidic tumor environment. In turn, MNPs may provide their transport capabilities under a
magnetic field. In this study it is proposed to use a mixture of both kinds of particles at two different
concentrations, trying to get the best from each of them. We study which mixture performs better from
different points of view, like stability and magnetic hyperthermia response, while keeping suitable
drug transport capabilities. This composite system is proposed as a close to ideal drug vehicle with
added enhanced hyperthermia response.We wish to thank FPU2016 grant (Ref. FPU16-04580), RYC-2014-6901 (MINECO, Spain), CGL2016-76723
(MINECO, Spain and FEDER, EU), Unidad Científica de Excelencia UCE-PP2016-05 (UGR) and Plan Propio Beca
de iniciación a la investigación para estudiantes de master (UGR)
Biomimetic Magnetic Nanocarriers Drive Choline Kinase Alpha Inhibitor inside Cancer Cells for Combined Chemo-Hyperthermia Therapy
Choline kinase a1 (ChoKa1) has become an excellent antitumor target. Among all the
inhibitors synthetized, the new compound Ff35 shows an excellent capacity to inhibit ChoKa1 activity.
However, soluble Ff35 is also capable of inhibiting choline uptake, making the inhibitor not selective
for ChoKa1. In this study, we designed a new protocol with the aim of disentangling whether the
Ff35 biological action is due to the inhibition of the enzyme and/or to the choline uptake. Moreover,
we offer an alternative to avoid the inhibition of choline uptake caused by Ff35, since the coupling
of Ff35 to novel biomimetic magnetic nanoparticles (BMNPs) allows it to enter the cell through
endocytosis without interacting with the choline transporter. This opens the possibility of a clinical
use of Ff35. Our results indicate that Ff35-BMNPs nanoassemblies increase the selectivity of Ff35 and
have an antiproliferative effect. Also, we demonstrate the effectiveness of the tandem Ff35-BMNPs
and hyperthermia.This research was funded by the Ministerio de Economía y Competitividad (CGL2013-46612 and
CGL2016-76723 projects), Ramón y Cajal programme (RYC-2014-16901) and the Fondo Europeo de Desarrollo
Regional (FEDER). Also, this research was aided by the Andalusian regional government (CTS-236)
Caracterización de nanosistemas magnéticos y su aplicación en quimioterapia dirigida y nanorremediación
Esta Tesis Doctoral ha sido realidad en el Departamento de Microbiología (Facultad de
Ciencias) de la Universidad de Granada durante los años 2015-2019 dentro del grupo de
investigación Mixobacterias.
Para realizar esta Tesis Doctoral la doctoranda ha disfrutado de:
Una ayuda para la Formación de Personal Investigador (F.P.I.) (BES-2014-
071206) a cargo del proyecto CGL2013-46612-P del Ministerio de Economía y
Competitividad, cuya investigadora principal es la Dra. Concepción Jiménez
López, Profesora Titular del Departamento de Microbiología de la Universidad
de Granada.
Cuatro ayudas para la realización de Estancias Breves (E.E.B.B.) en centros
extranjeros, con referencias: EEBB-I-16-11093 (92 días), EEBB-I-17-12558 (92
días), EEBB-I-18-12984 (102 días), EST2019-013134-I (60 días), también
financiadas por el Ministerio de Economía y Competitividad.Las nanopartículas de magnetita (Fe3O4) han despertado un gran interés en el
campo de la biotecnología debido a su alta relación superficie/volumen, que puede
utilizarse para anclar cantidades relativamente altas de moléculas específicas, y porque
pueden manipularse fácilmente utilizando un campo magnético externo, debido a su alto
momento magnético en comparación con otros óxidos de hierro. Se pueden sintetizar de
manera inorgánica utilizando diferentes procesos pero, generalmente, a altas
temperaturas y presiones, lo que implica altos costes de producción. Además, estas
magnetitas producidas químicamente no suelen presentar todas las características
deseables (alta magnetización, tamaños y morfologías adecuadas, biocompatibilidad o
alta estabilidad química) para ciertas aplicaciones biomédicas. Las bacterias
magnetotácticas (MTB) sintetizan magnetosomas, compuestos de Fe3O4 monocristalino
envuelto por una membrana, mediante un estricto control genético en el que intervienen
proteínas únicas llamadas proteínas asociadas a magnetosomas (MAPs). Este proceso de
biomineralización controlada (BCM) da como resultado nanopartículas de magnetita
con estructuras cristalinas perfectas, alta pureza química, morfologías alargadas y una
estrecha distribución de tamaños entre 30 y 120 nm, que hace que estos cristales sean de
dominio magnético único y, en consecuencia, la nanopartícula magnética ideal. Sin
embargo, no es posible escalar a nivel industrial el cultivo de MTB debido a sus
exigentes condiciones nutricionales y su lento crecimiento, por lo que los
magnetosomas no pueden obtenerse en grandes cantidades. De hecho, este es el cuello
de botella para la aplicación de los magnetosomas en nanotecnología. En este contexto,
una de las alternativas propuestas es la biomimética, es decir, la producción in vitro de
nanopartículas magnéticas similares a los magnetosomas mediante la utilización de
MAPs, dado que la interacción preferencial de MAPs con el cristal de magnetita se ha
sugerido para explicar las propiedades únicas de las magnetitas producidas por las
MTB. Sin embargo, todavía hay muchas incógnitas relacionadas con las estructuras y
funciones de la mayoría de las MAPs. Por lo tanto, desde un punto de vista biológico,
así como para la aplicación práctica de estas nanopartículas de magnetita biomiméticas
(BMNPs), comprender este proceso de BCM, el único conocido hasta ahora en el
dominio Bacteria, representa un desafío de extraordinaria importancia.Magnetite (Fe3O4) nanoparticles are of great interest in biotechnology field since
they have a large area surface, which can be used for anchoring relatively large amounts
of specific molecules, and can be easily manipulated by using an external magnetic field
because of their high magnetic moment per particle compared to other iron oxides. They
can be synthesized inorganically using different processes but, generally, performed at
high temperatures and pressures, which involves high costs of production. Moreover,
these chemically-produced magnetites usually do not have all desirable features (i.e.
high magnetization, consistent sizes and morphologies, biocompatibility or high
chemical stability) for certain biomedical applications. Magnetotactic bacteria (MTB)
synthesize magnetosomes comprised of membrane-enveloped single crystalline Fe3O4
by a strict genetic control in which are involved unique proteins called magnetosomeassociated
proteins (MAPs). This controlled biomineralization process (BCM) results in
nanomagnetites with perfect crystal structures, high chemical purity, elongated
morphologies and narrow size distribution (between 30 and 120 nm), making these
crystals a single magnetic domain and, in consequence, the ideal magnetic
nanoparticles. However, the scale up of such a production is not possible at present
because of the exigent nutrition conditions of MTB and their slow growth, so
magnetosomes cannot be obtained in large quantities. In fact, this is the bottleneck for
the application of magnetosomes in nanotechnology. In this context, one of the
proposed alternatives is biomimetic, i.e the in vitro production of magnetosome-like
magnetic nanoparticle mediated by MAPs, since preferential interaction of MAPs with
magnetite crystal has been suggested to explain the unique properties of the magnetites
produced by MTB. However, there are still many unknowns related to the structure and
function of most of the MAPs. So from a biological standpoint, as well as for the
potential application of this biomimetic magnetite nanoparticles (BMNPs),
understanding this BCM, the only one known so far in the domain Bacteria, represents a
challenge of extraordinary importance.Tesis Univ. Granada.CGL2013-46612-P del Ministerio de Economía y CompetitividadEEBB-I-16-11093 (92 días), EEBB-I-17-12558 (92 días), EEBB-I-18-12984 (102 días), EST2019-013134-I (60 días) Ministerio de Economía y Competitivida
Museo del aire en Cuatro Vientos [Hojas Resumen]
Museo del aire en Cuatro Viento
Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model
Simple Summary: The application of simultaneous and di erent strategies to treat cancer appears a
promising therapeutic approach. Herein we proposed the application of chemotherapy combined
with a magnetic nanocarrier delivery system to an in vitro and an in vivo experimental mammary
carcinoma model. Drug-loaded biomimetic magnetic nanoparticle can be directed and concentrated
on the tumor cells or site by the apposition of a magnet. Moreover, these nanoparticles can respond
to an alternating magnetic field by developing hyperthermia around 43 C, a temperature at which
tumor cells, but not healthy cells, are particularly sensitive and thus induced to death. Indeed,
when this nanoformulation is injected in vivo in the tumor site, and hyperthermia is generated,
the combined chemo-thermal therapy mediated by these drug-loaded magnetic nanoparticles have
a stronger therapeutic benefit compared to that carried out by the chemotherapeutic alone. These
nanoformulation and strategy are thus promising tools for translational applications in cancer therapy.
Abstract: Biomimetic magnetic nanoparticles mediated by magnetosome proteins (BMNPs) are
potential innovative tools for cancer therapy since, besides being multifunctional platforms, they can be
manipulated by an external gradient magnetic field (GMF) and/or an alternating magnetic field (AMF),
mediating targeting and hyperthermia, respectively. We evaluated the cytocompatibility/cytotoxicity
of BMNPs and Doxorubicin (DOXO)-BMNPs in the presence/absence of GMF in 4T1 and MCF-7
cells as well as their cellular uptake. We analyzed the biocompatibility and in vivo distribution
of BMNPs as well as the e ect of DOXO-BMNPs in BALB/c mice bearing 4T1 induced mammary carcinomas after applying GMF and AMF. Results: GMF enhanced the cell uptake of both BMNPs and
DOXO-BMNPs and the cytotoxicity of DOXO-BMNPs. BMNPs were biocompatible when injected
intravenously in BALB/c mice. The application of GMF on 4T1 tumors after each of the repeated
(6 ) iv administrations of DOXO-BMNPs enhanced tumor growth inhibition when compared to
any other treatment, including that with soluble DOXO. Moreover, injection of DOXO-BMNPs in
the tumor combined with application of an AMF resulted in a significant tumor weight reduction.
These promising results show the suitability of BMNPs as magnetic nanocarriers for local targeted
chemotherapy and as local agents for hyperthermia.Spanish Government
RYC-2014-16901Junta de Andalucía, Programa Operativo FEDER 2014-2020
A1-FQM-341-UGR18
C-FQM-497-UGR18Progetto di Ricerca Fondi di Ateneo per la Ricerca-FAR 2017 "Development of innovative biological materials for the functional regeneration of cardiac tissue models"Ministerio de Economia y Competitividad from Spain
CGL2016-76723European Union (EU)Junta de Andalucía
A-BIO-376-UGR18Unidad Científica de Excelencia of the University of Granada
UCE-PP2016-05Ministry of Economy and Competitiveness, Spain
EST2019-013134-I
EEBB-I-17-12558 5
The role of sleep and wakefulness in incidental language learning: one performance, two representations
info:eu-repo/semantics/nonPublishe
Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model
Simple Summary The application of simultaneous and different strategies to treat cancer appears a promising therapeutic approach. Herein we proposed the application of chemotherapy combined with a magnetic nanocarrier delivery system to an in vitro and an in vivo experimental mammary carcinoma model. Drug-loaded biomimetic magnetic nanoparticle can be directed and concentrated on the tumor cells or site by the apposition of a magnet. Moreover, these nanoparticles can respond to an alternating magnetic field by developing hyperthermia around 43 degrees C, a temperature at which tumor cells, but not healthy cells, are particularly sensitive and thus induced to death. Indeed, when this nanoformulation is injected in vivo in the tumor site, and hyperthermia is generated, the combined chemo-thermal therapy mediated by these drug-loaded magnetic nanoparticles have a stronger therapeutic benefit compared to that carried out by the chemotherapeutic alone. These nanoformulation and strategy are thus promising tools for translational applications in cancer therapy. Biomimetic magnetic nanoparticles mediated by magnetosome proteins (BMNPs) are potential innovative tools for cancer therapy since, besides being multifunctional platforms, they can be manipulated by an external gradient magnetic field (GMF) and/or an alternating magnetic field (AMF), mediating targeting and hyperthermia, respectively. We evaluated the cytocompatibility/cytotoxicity of BMNPs and Doxorubicin (DOXO)-BMNPs in the presence/absence of GMF in 4T1 and MCF-7 cells as well as their cellular uptake. We analyzed the biocompatibility and in vivo distribution of BMNPs as well as the effect of DOXO-BMNPs in BALB/c mice bearing 4T1 induced mammary carcinomas after applying GMF and AMF. Results: GMF enhanced the cell uptake of both BMNPs and DOXO-BMNPs and the cytotoxicity of DOXO-BMNPs. BMNPs were biocompatible when injected intravenously in BALB/c mice. The application of GMF on 4T1 tumors after each of the repeated (6x) iv administrations of DOXO-BMNPs enhanced tumor growth inhibition when compared to any other treatment, including that with soluble DOXO. Moreover, injection of DOXO-BMNPs in the tumor combined with application of an AMF resulted in a significant tumor weight reduction. These promising results show the suitability of BMNPs as magnetic nanocarriers for local targeted chemotherapy and as local agents for hyperthermia
The role of sleep and wakefulness in incidental statistical language learning: one performance, two representations
p. 12info:eu-repo/semantics/nonPublishe