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 99.9% of iron. The qualification of the bank as a PCB relies first on a preserved identity of the MTB compared with the original strain, second on genetic bacterial stability observed over 100 generations or under cryo-preservation for 16 months, third on a high level of purity highlighted by an absence of contaminating microorganisms in the PCB. Furthermore, the PCB was prepared under high-cell load conditions (9.108 cells/mL), allowing large-scale bacterial amplification and magnetosome production. In the future, the PCB could therefore be considered for commercial as well as research orientated applications in nanomedicine. We describe for the first-time conditions for setting-up an effective pharmaceutical cellular bank preserving over time the ability of certain specific cells, i.e. Magnetospirillum gryphiswaldense MSR1 MTB, to produce nano-minerals, i.e. magnetosomes, within a pharmaceutical setting.

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. To enable magnetosome medical applications, these growth media are reduced and amended compared with media commonly used to grow these bacteria. Furthermore, magnetosomes are made non-pyrogenic by being extracted from these micro-organisms and heated above 400 °C to remove and denature bacterial organic material and produce inorganic magnetosome minerals. To be stabilized, these minerals are further coated with citric acid to yield M-CA, leading to fully reconstructed chains of magnetosomes. The heating properties and anti-tumor activity of highly pure M-CA are then studied by bringing M-CA into contact with PC3-Luc tumor cells and by exposing such assembly to an alternating magnetic field (AMF) of 42 mT and 195 kHz during 30 min. While in the absence of AMF, M-CA are observed to be non-cytotoxic, they result in a 35% decrease in cell viability following AMF application. The treatment efficacy can be associated with a specific absorption rate (SAR) value of M-CA, which is relatively high in cellular environment, i.e., SARcell = 253 ± 11 W/gFe, while being lower than the M-CA SAR value measured in water, i.e., SARwater = 1025 ± 194 W/gFe, highlighting that a reduction in the Brownian contribution to the SAR value in cellular environment does not prevent efficient tumor cell destruction with these nanoparticles. KEY POINTS : • Highly pure magnetosomes were produced in pharmaceutically compatible growth media • Non-pyrogenic and stable magnetosomes were prepared for human injection • Magnetosomes efficiently destroyed prostate tumor cells in magnetic hyperthermia.

Ultrasound and nanomaterial: an efficient pair to fight cancer.

Ultrasounds are often used in cancer treatment protocols, e.g. to collect tumor tissues in the right location using ultrasound-guided biopsy, to image the region of the tumor using more affordable and easier to use apparatus than MRI and CT, or to ablate tumor tissues using HIFU. The efficacy of these methods can be further improved by combining them with various nano-systems, thus enabling: (i) a better resolution of ultrasound imaging, allowing for example the visualization of angiogenic blood vessels, (ii) the specific tumor targeting of anti-tumor chemotherapeutic drugs or gases attached to or encapsulated in nano-systems and released in a controlled manner in the tumor under ultrasound application, (iii) tumor treatment at tumor site using more moderate heating temperatures than with HIFU. Furthermore, some nano-systems display adjustable sizes, i.e. nanobubbles can grow into micro-bubbles. Such dual size is advantageous since it enables gathering within the same unit the targeting properties of nano bubbles via EPR effect and the enhanced ultrasound contrasting properties of micro bubbles. Interestingly, the way in which nano-systems act against a tumor could in principle also be adjusted by accurately selecting the nano-system among a large choice and by tuning the values of the ultrasound parameters, which can lead, due to their mechanical nature, to specific effects such as cavitation that are usually not observed with purely electromagnetic waves and can potentially help destroying the tumor. This review highlights the clinical potential of these combined treatments that can improve the benefit/risk ratio of current cancer treatments.

Nanomaterials as Ultrasound Theragnostic Tools for Heart Disease Treatment/Diagnosis.

A variety of different nanomaterials (NMs) such as microbubbles (MBs), nanobubbles (NBs), nanodroplets (NDs), and silica hollow meso-structures have been tested as ultrasound contrast agents for the detection of heart diseases. The inner part of these NMs is made gaseous to yield an ultrasound contrast, which arises from the difference in acoustic impedance between the interior and exterior of such a structure. Furthermore, to specifically achieve a contrast in the diseased heart region (DHR), NMs can be designed to target this region in essentially three different ways (i.e., passively when NMs are small enough to diffuse through the holes of the vessels supplying the DHR, actively by being associated with a ligand that recognizes a receptor of the DHR, or magnetically by applying a magnetic field orientated in the direction of the DHR on a NM responding to such stimulus). The localization and resolution of ultrasound imaging can be further improved by applying ultrasounds in the DHR, by increasing the ultrasound frequency, or by using harmonic, sub-harmonic, or super-resolution imaging. Local imaging can be achieved with other non-gaseous NMs of metallic composition (i.e., essentially made of Au) by using photoacoustic imaging, thus widening the range of NMs usable for cardiac applications. These contrast agents may also have a therapeutic efficacy by carrying/activating/releasing a heart disease drug, by triggering ultrasound targeted microbubble destruction or enhanced cavitation in the DHR, for example, resulting in thrombolysis or helping to prevent heart transplant rejection.

The Potential of Various Nanotechnologies for Coronavirus Diagnosis/Treatment Highlighted through a Literature Analysis.

With the current COVID-19 outbreak, it has become essential to develop efficient methods for the treatment and detection of this virus. Among the new approaches that could be tested, that relying on nanotechnology finds one of its main grounds in the similarity between nanoparticle (NP) and coronavirus (COV) sizes, which promotes NP-COV interactions. Since COVID-19 is very recent, most studies in this field have focused on other types of coronavirus than COVID-19, such as those involved in MERS or SARS diseases. Although their number is limited, they have led to promising results on various COV using a wide range of different types of nanosystems, e.g., nanoparticles, quantum dos, or nanoassemblies of polymers/proteins. Additional efforts deserve to be spent in this field to consolidate these findings. Here, I first summarize the different nanotechnology-based methods used for COV detection, i.e., optical, electrical, or PCR ones, whose sensitivity was improved by the presence of nanoparticles. Furthermore, I present vaccination methods, which comprise nanoparticles used either as adjuvants or as active principles. They often yield a better-controlled immune response, possibly due to an improved antigen presentation/processing than in non-nanoformulated vaccines. Certain antiviral approaches also took advantage of nanoparticle uses, leading to specific mechanisms such as the blocking of virus replication at the cellular level or the reduction of a COV induced apoptotic cellular death.

Natural Metallic Nanoparticles for Application in Nano-Oncology.

Here, the various types of naturally synthesized metallic nanoparticles, which are essentially composed of Ce, Ag, Au, Pt, Pd, Cu, Ni, Se, Fe, or their oxides, are presented, based on a literature analysis. The synthesis methods used to obtain them most often involve the reduction of metallic ions by biological materials or organisms, i.e., essentially plant extracts, yeasts, fungus, and bacteria. The anti-tumor activity of these nanoparticles has been demonstrated on different cancer lines. They rely on various mechanisms of action, such as the release of chemotherapeutic drugs under a pH variation, nanoparticle excitation by radiation, or apoptotic tumor cell death. Among these natural metallic nanoparticles, one type, which consists of iron oxide nanoparticles produced by magnetotactic bacteria called magnetosomes, has been purified to remove endotoxins and abide by pharmacological regulations. It has been tested in vivo for anti-tumor efficacy. For that, purified and stabilized magnetosomes were injected in intracranial mouse glioblastoma tumors and repeatedly heated under the application of an alternating magnetic field, leading to the full disappearance of these tumors. As a whole, the results presented in the literature form a strong basis for pursuing the efforts towards the use of natural metallic nanoparticles for cancer treatment first pre-clinically and then clinically.

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. 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.

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. However, their identification in ancient geological material remains challenging. Together with physical and mineralogical properties, the chemical composition of magnetite was proposed as a promising tracer for bacterial magnetofossil identification, but this had never been explored quantitatively and systematically for many trace elements. Here, we determine the incorporation of 34 trace elements in magnetite in both cases of abiotic aqueous precipitation and of production by the magnetotactic bacterium Magnetospirillum magneticum strain AMB-1. We show that, in biomagnetite, most elements are at least 100 times less concentrated than in abiotic magnetite and we provide a quantitative pattern of this depletion. Furthermore, we propose a previously unidentified method based on strontium and calcium incorporation to identify magnetite produced by magnetotactic bacteria in the geological record.

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. 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.

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 toxicity and efficiency of magnetosomes needs to be understood and the risk-benefit ratio with which to evaluate their use in the magnetic hyperthermia treatment of tumours needs to be measured.

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. The presence of iron-chelating agents also produced an increase in magnetosome size and chain length and yielded improved magnetosome heating properties. The specific absorption rate of suspensions of magnetosome chains isolated from M. magneticum strain AMB-1 magnetotactic bacteria, measured under the application of an alternating magnetic field of average field strength ∼20 mT and frequency 198 kHz, increased from ∼222 W/g(Fe) in the absence of iron-chelating agent up to ∼444 W/g(Fe) in the presence of 4 µM rhodamine B and to ∼723 W/g(Fe) in the presence of 4 µM EDTA. These observations were made at an iron concentration of 20 µM and iron-chelating agent concentrations below 40 µM.

Nano dimensions/adjuvants in COVID-19 vaccines.

A favorable outcome of the COVID-19 crisis might be achieved with massive vaccination. The proposed vaccines contain several different vaccine active principles (VAP), such as inactivated virus, antigen, mRNA, and DNA, which are associated with either standard adjuvants or nanomaterials (NM) such as liposomes in Moderna's and BioNTech/Pfizer's vaccines. COVID-19 vaccine adjuvants may be chosen among liposomes or other types of NM composed for example of graphene oxide, carbon nanotubes, micelles, exosomes, membrane vesicles, polymers, or metallic NM, taking inspiration from cancer nano-vaccines, whose adjuvants may share some of their properties with those of viral vaccines. The mechanisms of action of nano-adjuvants are based on the facilitation by NM of targeting certain regions of immune interest such as the mucus, lymph nodes, and zones of infection or blood irrigation, the possible modulation of the type of attachment of the VAP to NM, in particular VAP positioning on the NM external surface to favor VAP presentation to antigen presenting cells (APC) or VAP encapsulation within NM to prevent VAP degradation, and the possibility to adjust the nature of the immune response by tuning the physico-chemical properties of NM such as their size, surface charge, or composition. The use of NM as adjuvants or the presence of nano-dimensions in COVID-19 vaccines does not only have the potential to improve the vaccine benefit/risk ratio, but also to reduce the dose of vaccine necessary to reach full efficacy. It could therefore ease the overall spread of COVID-19 vaccines within a sufficiently large portion of the world population to exit the current crisis.

Light-Interacting iron-based nanomaterials for localized cancer detection and treatment.

To improve the prognosis of cancer patients, methods of local cancer detection and treatment could be implemented. For that, iron-based nanomaterials (IBN) are particularly well-suited due to their biocompatibility and the various ways in which they can specifically target a tumor, i.e. through passive, active or magnetic targeting. Furthermore, when it is needed, IBN can be associated with well-known fluorescent compounds, such as dyes, clinically approved ICG, fluorescent proteins, or quantum dots. They may also be excited and detected using well-established optical methods, relying on scattering or fluorescent mechanisms, depending on whether IBN are associated with a fluorescent compound or not. Systems combining IBN with optical methods are diverse, thus enabling tumor detection in various ways. In addition, these systems provide a wealth of information, which is inaccessible with more standard diagnostic tools, such as single tumor cell detection, in particular by combining IBN with near-field scanning optical microscopy, dark-field microscopy, confocal microscopy or super-resolution microscopy, or the highlighting of certain dynamic phenomena such as the diffusion of a fluorescent compound in an organism, e.g. using fluorescence lifetime imaging, fluorescence resonance energy transfer, fluorescence anisotropy, or fluorescence tomography. Furthermore, they can in some cases be complemented by a therapeutic approach to destroy tumors, e.g. when the fluorescent compound is a drug, or when a technique such as photo-thermal or photodynamic therapy is employed. This review brings forward the idea that iron-based nanomaterials may be associated with various optical techniques to form a commercially available toolbox, which can serve to locally detect or treat cancer with a better efficacy than more standard medical approaches. STATEMENT OF SIGNIFICANCE: New tools should be developed to improve cancer treatment outcome. For that, two closely-related aspects deserve to be considered, i.e. early tumor detection and local tumor treatment. Here, I present various types of iron-based nanomaterials, which can achieve this double objective when they interact with a beam of light under specific and accurately chosen conditions. Indeed, these materials are biocompatible and can be used/combined with most standard microscopic/optical methods. Thus, these systems enable on the one hand tumor cell detection with a high sensitivity, i.e. down to single tumor cell level, and on the other hand tumor destruction through various mechanisms in a controlled and localized manner by deciding whether or not to apply a beam of light and by having these nanomaterials specifically target tumor cells.

Bio-synthesized iron oxide nanoparticles for cancer treatment.

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.

Applications of magnetotactic bacteria and magnetosome for cancer treatment: A review emphasizing on practical and mechanistic aspects.

Magnetotactic bacteria (MTB) synthesize iron oxide (Fe3O4) nanoparticles (NPs), called magnetosomes, with large sizes leading to a ferrimagnetic behavior and a stable magnetic moment at physiological temperature, a chain structure that prevents NP aggregation and promotes uniform NP distribution, and a mineral core of magnetite/maghemite composition, which can be stabilized by an organic coating. Such properties can favor magnetosome administration to humans under certain optimized non-toxic conditions of fabrication. In this review, I describe the fabrication methods, physico-chemical properties, and the anti-tumor activity of different types of MTB/magnetosome preparations, highlighting the bio-compatibility and excellent anti-tumor activity of purified non-pyrogenic magnetosome minerals stabilized by a synthetic chemical compound.

Nano-Therapies for Glioblastoma Treatment.

Traditional anti-cancer treatments are inefficient against glioblastoma, which remains one of the deadliest and most aggressive cancers. Nano-drugs could help to improve this situation by enabling: (i) an increase of anti-glioblastoma multiforme (GBM) activity of chemo/gene therapeutic drugs, notably by an improved diffusion of these drugs through the blood brain barrier (BBB), (ii) the sensibilization of radio-resistant GBM tumor cells to radiotherapy, (iii) the removal by surgery of infiltrating GBM tumor cells, (iv) the restoration of an apoptotic mechanism of GBM cellular death, (v) the destruction of angiogenic blood vessels, (vi) the stimulation of anti-tumor immune cells, e.g., T cells, NK cells, and the neutralization of pro-tumoral immune cells, e.g., Treg cells, (vii) the local production of heat or radical oxygen species (ROS), and (viii) the controlled release/activation of anti-GBM drugs following the application of a stimulus. This review covers these different aspects.

Iron oxide nanoparticles for therapeutic applications.

In nanomedicine, iron oxide nanoparticles are at an advanced stage, being commercialized for cancer treatment and iron-deficiency anemia treatment. Their therapeutic efficacy comes from their ability to target a tissue, activate a drug, locally produce a temperature increase following (or not) the application of an external source of energy, modify genes or activate various biological materials, or replace diseased cells by stem cells. Owing to these various mechanisms of action, they can potentially be used for treating a whole range of different diseases, making them more appealing than conventional drugs that target a more limited number of indications.

A Method for Producing Highly Pure Magnetosomes in Large Quantity for Medical Applications Using Magnetospirillum gryphiswaldense MSR-1 Magnetotactic Bacteria Amplified in Minimal Growth Media.

We report the synthesis in large quantity of highly pure magnetosomes for medical applications. For that, magnetosomes are produced by MSR-1 Magnetospirillum gryphiswaldense magnetotactic bacteria using minimal growth media devoid of uncharacterized and toxic products prohibited by pharmaceutical regulation, i.e., yeast extract, heavy metals different from iron, and carcinogenic, mutagenic and reprotoxic agents. This method follows two steps, during which bacteria are first pre-amplified without producing magnetosomes and are then fed with an iron source to synthesize magnetosomes, yielding, after 50 h of growth, an equivalent OD565 of ~8 and 10 mg of magnetosomes in iron per liter of growth media. Compared with magnetosomes produced in non-minimal growth media, those particles have lower concentrations in metals other than iron. Very significant reduction or disappearance in magnetosome composition of zinc, manganese, barium, and aluminum are observed. This new synthesis method paves the way towards the production of magnetosomes for medical applications.

Iron oxide nanoparticles as multimodal imaging tools.

In medicine, obtaining simply a resolute and accurate image of an organ of interest is a real challenge. To achieve this, it has recently been proposed to use combined methods in which standard imaging (MRI, PAI, CT, PET/SPEC, USI, OI) is carried out in the presence of iron oxide nanoparticles, thus making it possible to image certain tissues/cells through the specific targeting of these nanoparticles, hence resulting in improved imaging contrast and resolution. Here, the advantages and drawbacks of these combined methods are presented as well as some of their recent medical applications.

Biodistribution and targeting properties of iron oxide nanoparticles for treatments of cancer and iron anemia disease.

IONP (iron oxide nanoparticles) commercialized for treatments of iron anemia or cancer diseases can be administered at doses exceeding 1 g per patient, indicating their bio-compatibility when they are prepared in the right conditions. Various parameters influence IONP biodistribution such as nanoparticle size, hydrophobicity/hydrophilicity, surface charge, core composition, coating properties, route of administration, quantity administered, and opsonization. IONP biodistribution trends include their capture by the reticuloendothelial system (RES), accumulation in liver and spleen, leading to nanoparticle degradation by macrophages and liver Kupffer cells, possibly followed by excretion in feces. To result in efficient tumor treatment, IONP need to reach the tumor in a sufficiently large quantity, using: (i) passive targeting, i.e. the extravasation of IONP through the blood vessel irrigating the tumor, (ii) molecular targeting achieved by a ligand bound to IONP specifically recognizing a cell receptor, and (iii) magnetic targeting in which a magnetic field gradient guides IONP towards the tumor. As a whole, targeting efficacy is relatively similar for different targeting, yielding a percentage of injected IONP in the tumor of 5.10-4% to 3%, 0.1% to 7%, and 5.10-3% to 2.6% for passive, molecular, and magnetic targeting, respectively. For the treatment of iron anemia disease, IONP are captured by the RES, and dissolved into free iron, which is then made available for the organism. For the treatment of cancer, IONP either deliver chemotherapeutic drugs to tumors, produce localized heat under the application of an alternating magnetic field or a laser, or activate in a controlled manner a sono-sensitizer following ultrasound treatment.