Stable pharmaceutical composition of cryo-protected non-pyrogenic isotonic chains of magnetosomes for efficient tumor cell destruction at 45 ± 1 °C under alternating magnetic field or ultrasound application.

We report a method to prepare biocompatible, stable, and highly pure iron oxide nano-minerals by following the steps consisting of: (i) amplifying magnetotactic bacteria in non-toxic minimal growth media; (ii) extracting magnetosomes from magnetotactic bacteria under alkaline lysis; (iii) heating magnetosomes above 400 °C to yield sterile magnetosome minerals, M-uncoated, devoid of active non-denatured bacterial organic material; (iv) coating M-uncoated with biocompatible carboxymethyl-dextran (CMD) compounds to yield stable M-CMD; (v) adding 5% sorbitol to M-CMD; and (vi) lyophilizing these mixtures, resulting in formulated nano-minerals in powder forms, designated as (M-CMD). The long-term stability of the final products is demonstrated by re-suspending (M-CMD) in water after 12 months of storage, and by showing that these formulated magnetosomes have preserved their stability in suspension, chain arrangement, carbon content, surface charge, and surface composition. Furthermore, the formulation is optimized to yield an isotonic magnetosome suspension with an osmolality of between 275 and 290 mOsm kg HO upon reconstitution.

Set-up of a pharmaceutical cell bank of Magnetospirillum gryphiswaldense MSR1 magnetotactic bacteria producing highly pure magnetosomes.

We report the successful fabrication of a pharmaceutical cellular bank (PCB) containing magnetotactic bacteria (MTB), which belong to the Magnetospirillum gryphiswaldense MSR1 species. To produce such PCB, we amplified MTB in a minimal growth medium essentially devoid of other heavy metals than iron and of CMR (Carcinogenic, mutagenic and reprotoxic) products. The PCB enabled to acclimate MTB to such minimal growth conditions and then to produce highly pure magnetosomes composed of more than 99.

Non-pyrogenic highly pure magnetosomes for efficient hyperthermia treatment of prostate cancer.

We report the fabrication of highly pure magnetosomes that are synthesized by magnetotactic bacteria (MTB) using pharmaceutically compatible growth media, i.e., without compounds of animal origin (yeast extracts), carcinogenic, mutagenic, or toxic for reproduction (CMR) products, and other heavy metals than iron.

Biodegraded magnetosomes with reduced size and heating power maintain a persistent activity against intracranial U87-Luc mouse GBM tumors.

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.

Fluorescent magnetosomes for controlled and repetitive drug release under the application of an alternating magnetic field under conditions of limited temperature increase (<2.5 °C).

Therapeutic substances bound to nanoparticles have been shown to dissociate following excitation by various external sources of energies or chemical disturbance, resulting in controllable and efficient antitumor activity. Bioconjugation is used to produce magnetosomes associated with Rhodamine B (RhB), whose fluorescence is partially quenched by the presence of iron oxide and becomes strongly enhanced when RhB dissociates from the magnetosomes under the application of an alternating magnetic field. This novel approach enables the release of a RhB model molecule while monitoring the mechanism by fluorescence.

Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma.

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).

Biocompatible coated magnetosome minerals with various organization and cellular interaction properties induce cytotoxicity towards RG-2 and GL-261 glioma cells in the presence of an alternating magnetic field.

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.

Nanoprobe Synthesized by Magnetotactic Bacteria, Detecting Fluorescence Variations under Dissociation of Rhodamine B from Magnetosomes following Temperature, pH Changes, or the Application of Radiation.

We report a method of fabrication of fluorescent magnetosomes, designated as MCR400, in which 400 μM of rhodamine B are introduced in the growth medium of AMB-1 magnetotactic bacteria and fluorescent magnetosomes are then extracted from these bacteria. These fluorescent magnetosomes behave differently from most fluorescent nanoprobes, which often lead to fluorescence losses over time due to photobleaching. Indeed, when MCR400 are heated to 30-90 °C, brought to an acidic pH, or exposed to radiations, we observed that their fluorescence intensity increased.

Biocompatible and stable magnetosome minerals coated with poly-l-lysine, citric acid, oleic acid, and carboxy-methyl-dextran for application in the magnetic hyperthermia treatment of tumors.

Magnetic hyperthermia, in which magnetic nanoparticles are introduced into tumors and exposed to an alternating magnetic field (AMF), appears to be promising since it can lead to increased life expectancy in patients. Its efficacy can be further improved by using biocompatible iron oxide magnetosome minerals with better crystallinity and magnetic properties compared with chemically synthesized nanoparticles (IONP - Iron Oxide Nanoparticles). To fabricate such minerals, magnetosomes are first isolated from MSR-1 magnetotactic bacteria, purified to remove potentially toxic organic bacterial residues and stabilized with poly-l-lysine (N-PLL), citric acid (N-CA), oleic acid (N-OA), or carboxy-methyl-dextran (N-CMD).

Chains of magnetosomes with controlled endotoxin release and partial tumor occupation induce full destruction of intracranial U87-Luc glioma in mice under the application of an alternating magnetic field.

Previous studies showed that magnetic hyperthermia could efficiently destroy tumors both preclinically and clinically, especially glioma. However, antitumor efficacy remained suboptimal and therefore required further improvements. Here, we introduce a new type of nanoparticles synthesized by magnetotactic bacteria, called magnetosomes, with improved properties compared with commonly used chemically synthesized nanoparticles.

Development of non-pyrogenic magnetosome minerals coated with poly-l-lysine leading to full disappearance of intracranial U87-Luc glioblastoma in 100% of treated mice using magnetic hyperthermia.

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.

Mass-dependent and -independent signature of Fe isotopes in magnetotactic bacteria.

Magnetotactic bacteria perform biomineralization of intracellular magnetite (Fe3O4) nanoparticles. Although they may be among the earliest microorganisms capable of biomineralization on Earth, identifying their activity in ancient sedimentary rocks remains challenging because of the lack of a reliable biosignature. We determined Fe isotope fractionations by the magnetotactic bacterium Magnetospirillum magneticum AMB-1.

Chemical signature of magnetotactic bacteria.

There are longstanding and ongoing controversies about the abiotic or biological origin of nanocrystals of magnetite. On Earth, magnetotactic bacteria perform biomineralization of intracellular magnetite nanoparticles under a controlled pathway. These bacteria are ubiquitous in modern natural environments.

Synthesis and biological evaluation of new bisphosphonate-dextran conjugates targeting breast primary tumor.

Bisphosphonates (BPs) have interesting antitumor effects as well in vitro as in vivo, despite their poor bioavailability in the organism after oral ingestion. To overcome this problem and reduce drug doses and secondary effects, we report the chemical synthesis of new bioconjugates. They were built with a nitrogen-containing BP as the drug covalently coupled to the carboxymethyldextran.

Use of bacterial magnetosomes in the magnetic hyperthermia treatment of tumours: a review.

We review the most recent and significant results published in the field of magnetotactic bacteria (MTB), in particular data relating to the use of bacterial magnetosomes in magnetic hyperthermia for the treatment of tumours. We review different methods for cultivating MTB and preparing suspensions of bacterial magnetosomes. As well as the production of magnetosomes, we also review key data on the toxicity of the magnetosomes as well as their heating and anti-tumour efficiencies.

The effect of iron-chelating agents on Magnetospirillum magneticum strain AMB-1: stimulated growth and magnetosome production and improved magnetosome heating properties.

The introduction of various iron-chelating agents to the Magnetospirillum magneticum strain AMB-1 bacterial growth medium stimulated the growth of M. magneticum strain AMB-1 magnetotactic bacteria and enhanced the production of magnetosomes. After 7 days of growth, the number of bacteria and the production of magnetosomes were increased in the presence of iron-chelating agents by factors of up to ∼2 and ∼6, respectively.

Preparation of chains of magnetosomes, isolated from Magnetospirillum magneticum strain AMB-1 magnetotactic bacteria, yielding efficient treatment of tumors using magnetic hyperthermia.

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.

Chains of magnetosomes extracted from AMB-1 magnetotactic bacteria for application in alternative magnetic field cancer therapy.

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.

A multimodal magnetic resonance imaging nanoplatform for cancer theranostics.

We describe an innovative multimodal system, which combines magnetic targeting of therapeutic agents with both magnetic resonance and fluorescence imaging into one system. This new magnetic nanoplatform consists of superparamagnetic γFe(2)O(3) nanoparticles, used clinically as an MRI contrast agent, conjugated to therapeutic molecules of the hydroxylmethylene bisphosphonate family (HMBPs): alendronate with an amine function as the terminal group. In vitro tests with breast cancer cells show that the γFe(2)O(3)@alendronate hybrid nanomaterial reduces cell viability and acts as a drug delivery system.

In vitro assessment of liposomal neridronate on MDA-MB-231 human breast cancer cells.

Bisphosphonates have been used for decades in the standard therapy of bone-related diseases, including bone metastasis of various malignancies, and they might as well be toxic on early cancer cells themselves. In order to allow a better delivery of neridronate (a N-containing bisphosphonate with relatively poor activity), liposomes were evaluated in vitro on cancer cell lines (MDA-MB-231, U87-MG and Caco2). After chemical synthesis, this water-soluble molecule was encapsulated into liposomes containing DOPC:DOPG:Chol (72:27:1 molar ratio).