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1.
ACS Appl Mater Interfaces ; 15(1): 566-577, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36563339

RESUMEN

Magnetotactic bacteria Magnetospirillum magneticum AMB-1 have been cultured using three different media: magnetic spirillum growth medium with Wolfe's mineral solution (MSGM + W), magnetic spirillum growth medium without Wolfe's mineral solution (MSGM - W), and flask standard medium (FSM). The influence of the culture medium on the structural, morphological, and magnetic characteristics of the magnetosome chains biosynthesized by these bacteria has been investigated by using transmission electron microscopy, X-ray absorption spectroscopy, and X-ray magnetic circular dichroism. All bacteria exhibit similar average size for magnetosomes, 40-45 nm, but FSM bacteria present slightly longer subchains. In MSGM + W bacteria, Co2+ ions present in the medium substitute Fe2+ ions in octahedral positions with a total Co doping around 4-5%. In addition, the magnetic response of these bacteria has been thoroughly studied as functions of both the temperature and the applied magnetic field. While MSGM - W and FSM bacteria exhibit similar magnetic behavior, in the case of MSGM + W, the incorporation of the Co ions affects the magnetic response, in particular suppressing the Verwey (∼105 K) and low temperature (∼40 K) transitions and increasing the coercivity and remanence. Moreover, simulations based on a Stoner-Wolhfarth model have allowed us to reproduce the experimentally obtained magnetization versus magnetic field loops, revealing clear changes in different anisotropy contributions for these bacteria depending on the employed culture medium. Finally, we have related how these magnetic changes affect their heating efficiency by using AC magnetometric measurements. The obtained AC hysteresis loops, measured with an AC magnetic field amplitude of up to 90 mT and a frequency, f, of 149 kHz, reveal the influence of the culture medium on the heating properties of these bacteria: below 35 mT, MSGM - W bacteria are the best heating mediators, but above 60 mT, FSM and MSGM + W bacteria give the best heating results, reaching a maximum heating efficiency or specific absorption rate (SAR) of SAR/f ≈ 12 W g-1 kHz-1.


Asunto(s)
Hipertermia Inducida , Magnetosomas , Magnetospirillum , Magnetospirillum/química , Magnetospirillum/metabolismo , Magnetosomas/química , Fenómenos Magnéticos
2.
J Mater Sci Mater Med ; 31(8): 75, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32761252

RESUMEN

Our study investigates the effect of magnetosome mediated oral Insulin delivery on diabetic induced rat models. The study involves the development of Magnetosome-Insulin (MI) conjugates by direct and indirect (by means of PEG) coupling method and further characterized by microscopic and spectroscopic analysis. The in vivo oral delivery of magnetosome-Insulin conjugate against streptozotocin-induced rat models and its efficiency was investigated. The impact of MI showed a remarkable change in the reduction of FBG levels up to 65% than the standard (Insulin). Similarly, the serum parameters: triglycerides (43.81%), AST&ALT (39.4 and 57.2%), total cholesterol (43.8%) showed significant changes compared to the diabetic control. The histological results of MI treated rats were found similar to control rats. Thus, these significantly notable results on diabetic rats depicts that magnetosomes can be employed as a potential approach and a very promising alternative for the parenteral route of Insulin delivery.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Portadores de Fármacos/química , Insulina/administración & dosificación , Magnetosomas/química , Administración Oral , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/farmacocinética , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Insulina/farmacocinética , Magnetosomas/metabolismo , Magnetospirillum/metabolismo , Masculino , Ratas , Ratas Wistar , Estreptozocina
3.
Int J Pharm ; 586: 119472, 2020 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-32590095

RESUMEN

Various living organisms, such as bacteria, plants, and animals can synthesize iron oxide nanoparticles (IONP). The mechanism of nanoparticle (NP) formation is usually described as relying on the reduction of ferric/ferrous iron ions into crystallized nanoparticulate iron that is surrounded by an organic stabilizing layer. The properties of these NP are characterized by a composition made of different types of iron oxide whose most stable and purest one appears to be maghemite, by a size predominantly comprised between 5 and 380 nm, by a crystalline core, by a surface charge which depends on the nature of the material coating the iron oxide, and by certain other properties such as a sterility, stability, production in mass, absence of aggregation, that have apparently only been studied in details for IONP synthesized by magnetotactic bacteria, called magnetosomes. In the majority of studies, bio-synthesized IONP are described as being biocompatible and as not inducing cytotoxicity towards healthy cells. Anti-tumor activity of bio-synthesized IONP has mainly been demonstrated in vitro, where this type of NP displayed cytotoxicity towards certain tumor cells, e.g. through the anti-tumor activity of IONP coating or through IONP anti-oxidizing property. Concerning in vivo anti-tumor activity, it was essentially highlighted for magnetosomes administered in different types of glioblastoma tumors (U87-Luc and GL-261), which were exposed to a series of alternating magnetic field applications, resulting in mild hyperthermia treatments at typical temperatures of 41-45 °C, leading to the full disappearance of these tumors without any observable side effects.


Asunto(s)
Campos Magnéticos , Nanopartículas Magnéticas de Óxido de Hierro/administración & dosificación , Neoplasias/terapia , Animales , Cristalización , Glioblastoma/terapia , Humanos , Hipertermia Inducida/métodos , Nanopartículas Magnéticas de Óxido de Hierro/efectos adversos , Magnetosomas/química , Tamaño de la Partícula
4.
J Nanobiotechnology ; 17(1): 126, 2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31870376

RESUMEN

BACKGROUND: An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS: When magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant magnetosome sizes within the magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION: Here, we report sustained magnetosome anti-tumor activity under conditions of significant magnetosome size reduction and complete loss of magnetosome heating power.


Asunto(s)
Antineoplásicos/química , Neoplasias Encefálicas/tratamiento farmacológico , Nanopartículas de Magnetita/química , Magnetosomas/química , Magnetospirillum/química , Animales , Línea Celular Tumoral , Supervivencia Celular , Femenino , Calefacción , Humanos , Hipertermia Inducida , Campos Magnéticos , Ratones , Ratones Desnudos , Tamaño de la Partícula , Nanomedicina Teranóstica/métodos , Distribución Tisular
5.
Small ; 15(41): e1902626, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31454160

RESUMEN

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.


Asunto(s)
Hipertermia Inducida , Campos Magnéticos , Magnetospirillum/fisiología , Células A549 , Supervivencia Celular , Fluorescencia , Humanos , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/ultraestructura , Magnetosomas/química , Magnetosomas/ultraestructura , Magnetospirillum/ultraestructura , Temperatura , Factores de Tiempo
6.
Sci Rep ; 9(1): 8804, 2019 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-31217514

RESUMEN

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 applications.


Asunto(s)
Proteínas Bacterianas/metabolismo , Materiales Biomiméticos/química , Nanopartículas de Magnetita/química , Magnetosomas/química , Alphaproteobacteria/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Simulación por Computador , Nanopartículas de Magnetita/ultraestructura , Magnetosomas/ultraestructura
7.
ACS Appl Mater Interfaces ; 10(44): 37898-37910, 2018 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-30360046

RESUMEN

Magnetosomes represent magnetic nanoparticles with unprecedented characteristics. Both their crystal morphology and the composition of the enveloping membrane can be manipulated by genetic means, allowing the display of functional moieties on the particle surface. In this study, we explore the generation of a new biomaterial assembly by coupling magnetosomes with tobacco mosaic virus (TMV) particles, both functionalized with complementary recognition sites. TMV consists of single-stranded RNA encapsidated by more than 2100 coat proteins, which enable chemical modification via functional groups. Incubation of EmGFP- or biotin-decorated TMV particles with magnetosomes genetically functionalized with GFP-binding nanobodies or streptavidin, respectively, results in the formation of magnetic, mesoscopic, strand-like biocomposites. TMV facilitates the agglomeration of magnetosomes by providing a scaffold. The size of the TMV-magnetosome mesostrands can be adjusted by varying the TMV-magnetosome particle ratios. The versatility of this novel material combination is furthermore demonstrated by coupling magnetosomes and terminal, 5'-functionalized TMV particles with high molecular precision, which results in "drumstick"-like TMV-magnetosome complexes. In summary, our approaches provide promising strategies for the generation of new biomaterial assemblies that could be used as scaffold for the introduction of further functionalities, and we foresee a broad application potential in the biomedical and biotechnological field.


Asunto(s)
Materiales Biocompatibles/química , Magnetosomas/química , ARN Viral/química , Virus del Mosaico del Tabaco/química , Materiales Biocompatibles/síntesis química , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Magnetosomas/genética , ARN Viral/genética , Virus del Mosaico del Tabaco/genética
8.
Theranostics ; 7(18): 4618-4631, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29158849

RESUMEN

In this study, biologically synthesized iron oxide nanoparticles, called magnetosomes, are made fully biocompatible by removing potentially toxic organic bacterial residues such as endotoxins at magnetosome mineral core surfaces and by coating such surface with poly-L-lysine, leading to magnetosomes-poly-L-lysine (M-PLL). M-PLL antitumor efficacy is compared with that of chemically synthesized iron oxide nanoparticles (IONPs) currently used for magnetic hyperthermia. M-PLL and IONPs are tested for the treatment of glioblastoma, a dreadful cancer, in which intratumor nanoparticle administration is clinically relevant, using a mouse allograft model of murine glioma (GL-261 cell line). A magnetic hyperthermia treatment protocol is proposed, in which 25 µg in iron of nanoparticles per mm3 of tumor are administered and exposed to 11 to 15 magnetic sessions during which an alternating magnetic field of 198 kHz and 11 to 31 mT is applied for 30 minutes to attempt reaching temperatures of 43-46 °C. M-PLL are characterized by a larger specific absorption rate (SAR of 40 W/gFe compared to 26 W/gFe for IONPs as measured during the first magnetic session), a lower strength of the applied magnetic field required for reaching a target temperature of 43-46 °C (11 to 27 mT compared with 22 to 31 mT for IONPs), a lower number of mice re-administered (4 compared to 6 for IONPs), a longer residence time within tumours (5 days compared to 1 day for IONPs), and a less scattered distribution in the tumour. M-PLL lead to higher antitumor efficacy with full tumor disappearances achieved in 50% of mice compared to 20% for IONPs. This is ascribed to better ability of M-PLL, at equal iron concentrations, to maintain tumor temperatures at 43-46°C over a longer period of times.


Asunto(s)
Glioblastoma/terapia , Magnetosomas/química , Animales , Línea Celular Tumoral , Femenino , Glioblastoma/química , Glioma/terapia , Hipertermia Inducida/métodos , Campos Magnéticos , Ratones , Nanomedicina/métodos , Nanopartículas/química
9.
J Nanobiotechnology ; 15(1): 74, 2017 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-29041937

RESUMEN

BACKGROUND: Biologics magnetics nanoparticles, magnetosomes, attract attention because of their magnetic characteristics and potential applications. The aim of the present study was to develop and characterize novel magnetosomes, which were extracted from magnetotactic bacteria, purified to produce apyrogen magnetosome minerals, and then coated with Chitosan, Neridronate, or Polyethyleneimine. It yielded stable magnetosomes designated as M-Chi, M-Neri, and M-PEI, respectively. Nanoparticle biocompatibility was evaluated on mouse fibroblast cells (3T3), mouse glioblastoma cells (GL-261) and rat glioblastoma cells (RG-2). We also tested these nanoparticles for magnetic hyperthermia treatment of tumor in vitro on two tumor cell lines GL-261 and RG-2 under the application of an alternating magnetic field. Heating, efficacy and internalization properties were then evaluated. RESULTS: Nanoparticles coated with chitosan, polyethyleneimine and neridronate are apyrogen, biocompatible and stable in aqueous suspension. The presence of a thin coating in M-Chi and M-PEI favors an arrangement in chains of the magnetosomes, similar to that observed in magnetosomes directly extracted from magnetotactic bacteria, while the thick matrix embedding M-Neri leads to structures with an average thickness of 3.5 µm2 per magnetosome mineral. In the presence of GL-261 cells and upon the application of an alternating magnetic field, M-PEI and M-Chi lead to the highest specific absorption rates of 120-125 W/gFe. Furthermore, while M-Chi lead to rather low rates of cellular internalization, M-PEI strongly associate to cells, a property modulated by the application of an alternating magnetic field. CONCLUSIONS: Coating of purified magnetosome minerals can therefore be chosen to control the interactions of nanoparticles with cells, organization of the minerals, as well as heating and cytotoxicity properties, which are important parameters to be considered in the design of a magnetic hyperthermia treatment of tumor.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/uso terapéutico , Glioma/terapia , Magnetosomas/química , Nanopartículas/química , Nanopartículas/uso terapéutico , Células 3T3 , Animales , Línea Celular Tumoral , Quitosano/química , Quitosano/uso terapéutico , Difosfonatos/química , Difosfonatos/uso terapéutico , Hipertermia Inducida , Campos Magnéticos , Magnetospirillum/química , Ratones , Polietileneimina/química , Polietileneimina/uso terapéutico , Ratas
10.
Biomaterials ; 141: 210-222, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28689117

RESUMEN

Magnetic hyperthermia was reported to increase the survival of patients with recurrent glioblastoma by 7 months. This promising result may potentially be further improved by using iron oxide nanoparticles, called magnetosomes, which are synthesized by magnetotactic bacteria, extracted from these bacteria, purified to remove most endotoxins and organic material, and then coated with poly-l-lysine to yield a stable and non-pyrogenic nanoparticle suspension. Due to their ferrimagnetic behavior, high crystallinity and chain arrangement, these magnetosomes coated with poly-l-lysine (M-PLL) are characterized by a higher heating power than their chemically synthesized counterparts currently used in clinical trials. M-PLL-enhanced antitumor efficacy was demonstrated by administering 500-700 µg in iron of M-PLL to intracranial U87-Luc tumors of 1.5 mm3 and by exposing mice to 27 magnetic sessions each lasting 30 min, during which an alternating magnetic field of 202 kHz and 27 mT was applied. Treatment conditions were adjusted to reach a typical hyperthermia temperature of 42 °C during the first magnetic session. In 100% of treated mice, bioluminescence due to living glioblastoma cells fully disappeared 68 days following tumor cell implantation (D68). These mice were all still alive at D350. Histological analysis of their brain tissues revealed an absence of tumor cells, suggesting that they were fully cured. In comparison, antitumor efficacy was less pronounced in mice treated by the administration of IONP followed by 23 magnetic sessions, leading to full tumor bioluminescence disappearance in only 20% of the treated mice.


Asunto(s)
Neoplasias Encefálicas/terapia , Materiales Biocompatibles Revestidos/uso terapéutico , Óxido Ferrosoférrico/uso terapéutico , Glioblastoma/terapia , Hipertermia Inducida/métodos , Magnetosomas/química , Polilisina/uso terapéutico , Células 3T3 , Animales , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/química , Femenino , Óxido Ferrosoférrico/química , Glioblastoma/patología , Humanos , Campos Magnéticos , Magnetosomas/ultraestructura , Magnetospirillum/química , Ratones , Ratones Desnudos , Polilisina/análogos & derivados
11.
Biochim Biophys Acta Gen Subj ; 1861(6): 1507-1514, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28093197

RESUMEN

BACKGROUND: The magnetosome biosynthesis is a genetically controlled process but the physical properties of the magnetosomes can be slightly tuned by modifying the bacterial growth conditions. METHODS: We designed two time-resolved experiments in which iron-starved bacteria at the mid-logarithmic phase are transferred to Fe-supplemented medium to induce the magnetosomes biogenesis along the exponential growth or at the stationary phase. We used flow cytometry to determine the cell concentration, transmission electron microscopy to image the magnetosomes, DC and AC magnetometry methods for the magnetic characterization, and X-ray absorption spectroscopy to analyze the magnetosome structure. RESULTS: When the magnetosomes synthesis occurs during the exponential growth phase, they reach larger sizes and higher monodispersity, displaying a stoichiometric magnetite structure, as fingerprinted by the well defined Verwey temperature. On the contrary, the magnetosomes synthesized at the stationary phase reach smaller sizes and display a smeared Verwey transition, that suggests that these magnetosomes may deviate slightly from the perfect stoichiometry. CONCLUSIONS: Magnetosomes magnetically closer to stoichiometric magnetite are obtained when bacteria start synthesizing them at the exponential growth phase rather than at the stationary phase. GENERAL SIGNIFICANCE: The growth conditions influence the final properties of the biosynthesized magnetosomes. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.


Asunto(s)
Magnetosomas/metabolismo , Magnetospirillum/crecimiento & desarrollo , Magnetospirillum/metabolismo , Citometría de Flujo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Magnetosomas/química , Magnetosomas/ultraestructura , Magnetospirillum/ultraestructura , Microscopía Electrónica de Transmisión , Estructura Molecular , Tamaño de la Partícula , Factores de Tiempo , Espectroscopía de Absorción de Rayos X
12.
Int J Nanomedicine ; 11: 5277-5286, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27822032

RESUMEN

To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy. Doxorubicin (DOX) and pHSP70-Plk1-shRNA were included in the targeted thermosensitive co-delivery system, and in vitro DOX release activity, targeted gene silencing efficiency and in vitro antitumor efficacy were investigated. The results showed that the optimal culture conditions of MTB AMB-1 are an oxygen concentration of 4.0%, a pH value of 7.0, 20 µmol/L of ferrous sulfate, 800 mg/L of sodium nitrate, and 200 mg/L of succinic acid. The temperature of BMs reached 43°C within 3 minutes and could be maintained for 30 minutes by adjusting the magnitude of the alternating magnetic field (AMF). The diameters of BMs, BM-DOX, BM-recombinant eukaryotic plasmid pHSP70-Plk1-shRNA (shPlk1), and BM-DOX-shPlk1 were 43.7±4.6, 79.2±5.4, 88.9±7.8, and 133.5±11.4 nm, respectively. The zeta potentials of BMs, BM-DOX, BM-shPlk1, and BM-DOX-shPlk1 were -29.4±6.9, -9.5±5.6, -16.7±4.8, and -10.3±3.1 mV, respectively. Besides, the system exhibited good release behavior. DOX release rate from BM-DOX-shPlk1 was 54% after incubation with phosphate-buffered saline at 43°C and 37% after incubation with 50% fetal bovine serum, which was significantly higher than that at 37°C (P<0.05). In addition, the expressions of Plk1 mRNA and protein were significantly suppressed in cells treated with BM-DOX-shPlk1 following hyperthermia treatment under the influence of an AMF compared to other groups (P<0.05). Furthermore, evaluation of the effect of in vitro antitumor revealed that BM-DOX-shPlk1 following hyperthermia treatment under the influence of an AMF was significantly more effective than others in tumor inhibition. In conclusion, the new heat-sensitive co-delivery system represents a promising approach for the treatment of cancer.


Asunto(s)
Neoplasias Óseas/metabolismo , Doxorrubicina/administración & dosificación , Terapia Genética/métodos , Magnetosomas/química , Osteosarcoma/metabolismo , ARN Interferente Pequeño/genética , Apoptosis , Bacterias/metabolismo , Proteínas de Ciclo Celular/administración & dosificación , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular , Citometría de Flujo , Silenciador del Gen/efectos de los fármacos , Proteínas del Choque Térmico HSP72/metabolismo , Humanos , Hipertermia Inducida/métodos , Oxígeno/química , Plásmidos/metabolismo , Proteínas Serina-Treonina Quinasas/administración & dosificación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/administración & dosificación , Proteínas Proto-Oncogénicas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Recombinantes/química , Temperatura , Quinasa Tipo Polo 1
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2015: 3541-4, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26737057

RESUMEN

Biodegradable polymer droplet containing natural magnetic nanoparticle is composed for smart drug delivery and heat treatment. For selective and efficient drug delivery to the target tissue, direct high magnetic field will be applied near the target tissue. For drug release control and heat treatment, alternative high magnetic field will be applied. Magnetosome, natural magnetic nanoparticle, is extracted from magnetotactic bacteria, AMB-1. Mixture of magnetosome and sodium alginate composes into droplet using the microfluidic device applied Plateau-Rayleigh instability principle. The magnetosome contained droplet selected its rout at the bifurcate microchannels by direct high magnetic field. High alternative magnetic field generating circuit is designed with 18 mT and 4 Hz magnetic wave. The generated magnetic wave was applied to the extracted magnetosomes so that temperature of the magnetosomes increased from 15.2°C to 17.6°C.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Nanopartículas de Magnetita/química , Magnetosomas/química , Alginatos/química , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Calor , Hipertermia Inducida/métodos , Dispositivos Laboratorio en un Chip , Campos Magnéticos , Nanopartículas de Magnetita/administración & dosificación
14.
PLoS One ; 9(10): e108959, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25289664

RESUMEN

Magnetic nanoparticles (MNPs) are capable of generate heating power under the influence of alternating magnetic fields (AMF); this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs): a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI) to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias del Colon/patología , Nanopartículas de Magnetita/administración & dosificación , Magnetospirillum , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/tratamiento farmacológico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Células HT29 , Humanos , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Magnetosomas/química , Magnetosomas/metabolismo , Masculino , Ratones , Termodinámica
15.
Sci Rep ; 3: 1652, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23576006

RESUMEN

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies.


Asunto(s)
Materiales Biomiméticos/química , Materiales Biomiméticos/efectos de la radiación , Hipertermia Inducida/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Magnetosomas/química , Magnetosomas/efectos de la radiación , Calor , Campos Magnéticos , Nanopartículas de Magnetita/efectos de la radiación , Ensayo de Materiales , Dosis de Radiación
16.
Int J Pharm ; 434(1-2): 444-52, 2012 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-22698862

RESUMEN

Chains of magnetosomes isolated from Magnetospirillum magneticum strain AMB-1 magnetotactic bacteria by sonication at 30 W during 2 h are tested for magnetic hyperthermia treatment of tumors. These chains are composed of magnetosomes, which are bound to each other by a filament made of proteins. When they are incubated in the presence of cancer cells and exposed to an alternating magnetic field of frequency 198 kHz and average magnetic field strength of 20 or 30 mT, they produce efficient inhibition of cancer cell proliferation. This behavior is explained by a high cellular internalization, a good stability in solution and a homogenous distribution of the magnetosome chains, which enables efficient heating. When the chains are heated during 5 h at 90°C in the presence of 1% SDS, the filament binding the magnetosomes together is denatured and individual magnetosomes are obtained. By contrast to the chains of magnetosomes, the individual magnetosomes are prone to aggregation, are not stable in solution and do not produce efficient inhibition of cancer cell proliferation under application of an alternating magnetic field.


Asunto(s)
Hipertermia Inducida/métodos , Campos Magnéticos , Magnetosomas/química , Neoplasias/terapia , Línea Celular Tumoral , Proliferación Celular , Células HeLa , Calor , Humanos , Magnetospirillum/química , Neoplasias/patología , Sonicación
17.
ACS Nano ; 5(8): 6279-96, 2011 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-21732678

RESUMEN

Chains of magnetosomes extracted from AMB-1 magnetotactic bacteria are shown to be highly efficient for cancer therapy when they are exposed to an alternative magnetic field. When a suspension containing MDA-MB-231 breast cancer cells was incubated in the presence of various amounts of extracted chains of magnetosomes, the viability of these cells remained high in the absence of an alternative magnetic field. By contrast, when this suspension was exposed to an alternative magnetic field of frequency 183 kHz and field strengths of 20, 40, or 60 mT, up to 100% of these cells were destroyed. The antitumoral activity of the extracted chains of magnetosomes is demonstrated further by showing that they can be used to fully eradicate a tumor xenografted under the skin of a mouse. For that, a suspension containing ∼1 mg of extracted chains of magnetosomes was administered within the tumor and the mouse was exposed to three heat cycles of 20 min, during which the tumor temperature was raised to ∼43 °C. We also demonstrate the higher efficiency of the extracted chains of magnetosomes compared with various other materials, i.e., whole inactive magnetotactic bacteria, individual magnetosomes not organized in chains, and two different types of chemically synthesized superparamagnetic iron oxide nanoparticles currently tested for alternative magnetic field cancer therapy. The higher efficiency of the extracted chains of magnetosomes compared with that of the other nanoparticles is attributed to three factors: (i) a specific absorption rate higher for the magnetosomes than for the chemically synthesized superparamagnetic iron oxide nanoparticles, (ii) a more uniform heating for the chains of magnetosomes than for the individual magnetosomes and (iii) the ability of the chains of magnetosomes to penetrate within the cancer cells or bind at the cell membrane following the application of the alternative magnetic field, which enables efficient cell destruction. Biodistribution studies revealed that extracted chains of magnetosomes administered directly within xenografted breast tumors progressively left the tumors during the 14 days following their administration and were then eliminated in large proportion in the feces.


Asunto(s)
Bacterias/citología , Neoplasias de la Mama/terapia , Magnetoterapia/métodos , Magnetosomas , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Ácido Cítrico/química , Ácido Edético/química , Femenino , Calor , Humanos , Magnetosomas/química , Ratones , Nanopartículas/química , Nanopartículas/uso terapéutico , Polietilenglicoles/química , Dodecil Sulfato de Sodio/farmacología , Factores de Tiempo
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