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Cervical cancer is the fourth most common malignancy among women. Compared to other types of cancer, therapeutic agents can be administrated locally at the mucosal vaginal membrane. Thermosensitive gels have been developed over the years for contraception or for the treatment of bacterial, fungal, and sexually transmitted infections. These formulations often carry therapeutic nanoparticles and are now being considered in the arsenal of tools for oncology. They can also be three-dimensionally (3D) printed for a better geometrical adjustment to the anatomy of the patient, thus enhancing the local delivery treatment. In this study, a localized delivery system composed of a Pluronic F127-alginate hydrogel with efficient nanoparticle (NP) release properties was prepared for intravaginal application procedures. The kinetics of hydrogel degradation and its NP releasing properties were demonstrated with ultrasmall gold nanoparticles (∼80% of encapsulated AuNPs released in 48 h). The mucoadhesive properties of the hydrogel formulation were assayed by the periodic acid/Schiff reagent staining, which revealed that 19% of mucins were adsorbed on the gel's surface. The hydrogel formulation was tested for cytocompatibility in three cell lines (HeLa, CRL 2616, and BT-474; no sign of cytotoxicity revealed). The release of AuNPs from the hydrogel and their accumulation in vaginal membranes were quantitatively measured

In this exploratory work, micrometric radiopaque W–Fe–Mn–C coatings were produced by magnetron sputtering plasma deposition, for the first time, with the aim to make very thin Fe–Mn stents trackable by fluoroscopy. The power of Fe–13Mn-1.2C target was kept constant at 400 W while that of W target varied from 100 to 400 W producing three different coatings referred to as P100, P200, P400. The effect of the increased W power on coatings thickness, roughness, structure, corrosion behavior and radiopacity was investigated. The coatings showed a power-dependent thickness and W concentration, different roughness values while a similar and uniform columnar structure. An amorphous phase was detected for both P100 and P200 coatings while γ-Fe, bcc-W and W3C phases found for P400. Moreover, P200 and P400 showed a significantly higher corrosion rate (CR) compared to P100. The presence of W, W3C as well as the Fe amount variation determined two different micro-galvanic corrosion mechanisms significantly changing the CR of coatings, 0.26 ± 0.02, 59.68 ± 1.21 and 59.06 ± 1.16 μm/year for P100, P200 and P400, respectively. Sample P200 with its most uniform morphology, lowest roughness (RMS = 3.9 ± 0.4 nm) and good radiopacity (∼6%) appeared the most suitable radiopaque biodegradable coating investigated in this study., Graphical abstract Image 1, Highlights • Three W–Fe–Mn–C coatings (P100, P200, P400) were developed by magnetron sputtering. • Coatings showed a columnar structure and power-dependent thickness and W concentration. • Thicknesses from 0.9 ± 0.2 to 1.8 ± 0.2 μm and RMS from 3.9 ± 0.4 to 54.3 ± 8.1 nm were found for P100, P200, P400, resp. • The amorphous phase of P100, P200 and γ-Fe, bcc-W and W3C of P400 significantly affected the CR. • The most uniform morphology, lowest roughness (3.9 ± 0.4 nm) and good radiopacity (∼6%) were found for P200.

Diffusion cells are devices made of donor and acceptor compartments (DC and AC), separated by a membrane. They are widely used in pharmaceutical, cosmetic, toxicology, and protective equipment tests (e.g., gloves) to measure the kinetics of permeants (molecules and nanoparticles) across biological membranes as the skin. However, rarely is the concentration of permeants in the AC measured in continuous or in real-time, and this limitation leads to significant discrepancies in the calculations of kinetic parameters that define the permeation mechanisms. In this study, a diffusion cell compatible with positron emission tomography was used to measure the permeation kinetics of nanoparticles across glove membranes. The technology allows for the measurement of nanoparticle concentration in real-time in the two compartments (DC and AC) and at a detection sensitivity several orders of magnitude higher compared with conventional spectroscopies, thus allowing a much more precise extraction of kinetic parameters. Ultra-small (

Diffusion cells are routinely used in pharmacology to measure the permeation of pharmaceutical compounds and contaminants across membranes (biological or synthetic). They can also be used to study drug release from excipients. The device is made of a donor (DC) and an acceptor (AC) compartment, separated by a membrane. Usually, permeation of molecules across membranes is measured by sampling from the AC at different time points. However, this process disturbs the equilibrium of the cell. Furthermore, analytical techniques used in association with diffusion cells sometimes lack either accuracy, sensitivity, or both. This work reports on the development of nuclear imaging – compatible diffusion cells. The cell is made of a polymer transparent to high-energy photons typically detected in positron emission tomography (PET). It was tested in a finite-dose set-up experiment with a pre-clinical PET system. Porous cellulose membranes (3.5, 25 and 300 kDa), a common excipient in pharmacology, as well as for dialysis membranes, were used as test membranes. The radioisotope 89Zr chelated with deferoxamine B (DFO; 0.65 kDa), was used as an imaging probe (7–10 MBq; 0.2–0.3 nMol 89Zr-DFO). In medicine, DFO is also commonly used for iron removal treatments and pharmacological formulations often require the association of this molecule with cellulose. Permeation profiles were obtained by measuring the radioactivity in the DC and AC for up to 2 weeks. The kinetic profiles were used to extract lag time, influx, and diffusion coefficients of DFO across porous cellulose membranes. A sensitivity threshold of 0.005 MBq, or 3.4 fmol of 89Zr-DFO, was revealed. The lag time to permeation (τ) measured in the AC compartment, was found to be 1.33, 0.5, and 0.19 h with 3.5, 25, and 300 kDa membranes, respectively. Diffusion coefficients of 3.65 × 10−6, 8.33 × 10−6, and 4.74 × 10−5 cm2 h−1 where revealed, with maximal pseudo steady-state influx values (Jpss) of 6.55 × 10−6, 1.76 × 10−5, and 1.29 × 10−5 nmol cm−2 h−1. This study confirms the potential of the technology for monitoring molecular diffusion and release processes at low concentrations, high sensitivities, in real time and in a visual manner.

Ultrasmall nanoparticles (US-NPs

Microencapsulation is being investigated as a means to avoid rejection of transplanted pancreatic islets. Monitoring bead distribution and stability in vivo is an important step toward improving microencapsulated islet transplantation strategies. Islet co-encapsulation with gadolinium-labeled mesoporous silica nanoparticles (Gd-MSNs) could allow bead visualization while immobilizing and limiting the potential internalization of the contrast agent. The porous nature of the MSNs could also be used to locally release anti-inflammatory, angiogenic, or anti-apoptotic factors. Mouse insulinoma 6 (MIN6) beta cells were co-encapsulated with Gd-MSNs in alginate beads produced by emulsification and internal gelation. Gd-MSN alginate beads appeared brighter in T1-weighted imaging sequences (detection threshold of 0.016 mM Gd; relaxometric ratio r2/r1 = 1.45) than beads without Gd-MSNs. No leaching of Gd3+ from the hydrogels was detected over the course of 3 months. MIN6 cells co-encapsulated with Gd-MSNs were viable...

Brain microvessel endothelial cells (BMECs) are the main structural and dynamic components of the blood–brain barrier (BBB), preventing the majority of drugs from reaching the brain. Since BMECs are involved in a wide range of central nervous system diseases, the development of nanocarriers that trigger receptor-mediated uptake in these cells has been suggested as a promising approach to an increased drug delivery to the brain. Here, we report the size and the bioconjugation effects of antibody-conjugated mesoporous silica nanoparticles (MSNs) on in vitro and in vivo targeting ability to BMECs. For this, Ri7 antibody was conjugated to MSNs of two different sizes (50 nm and 160 nm in diameter) through a polyethylene glycol (PEG) linker. The particles were also functionalized with a MRI contrast agent (gadolinium chelate) and with a fluorescent label. The functionalized MSN suspensions showed good colloidal stability. The Ri7 antibody immobilized on the MSN surface maintained its high specific activity and high binding affinity, as demonstrated in vitro. Cells incubated with gadolinium-chelated Ri7-MSNs showed a significant MRI positive contrast enhancement, highlighting the potential of such nanoparticles for theranostic applications. To measure the uptake and affinity of Ri7-MSNs to brain endothelial and neuronal cells, cell uptake studies were performed and a quantitative cellular assay was developed. The results revealed that endocytosis of nanoparticles is mediated by transferrin receptors and that Ri7-MSN cellular uptake is size- and time-dependent. A highest specific uptake was found with 50 nm Ri7-MSNs. Upon intravenous injection, 50 nm Ri7-MSNs were specifically accumulated in BMECs, suggesting the strong potential of antibody-coated nanoparticles for targeting BMECs in vivo. These findings open the door to therapeutic targeting of BMECs, enabling potential therapeutic drug delivery to the brain.

Gold nanoparticles (Au NPs) distributed in the vicinity of low-dose rate (LDR) brachytherapy seeds could multiply their efficacy thanks to the secondary emissions induced by the photoelectric effect. Injections of radioactive LDR gold nanoparticles (LDR Au NPs), instead of conventional millimeter-size radioactive seeds surrounded by Au NPs, could further enhance the dose by distributing the radioactivity more precisely and homogeneously in tumors. However, the potential of LDR Au NPs as an emerging strategy to treat cancer is strongly dependent on the macroscopic diffusion of the NPs in tumors, as well as on their microscopic internalization within the cells. Understanding the relationship between interstitial and intracellular distribution of NPs, and the outcomes of dose deposition in the cancer tissue is essential for considering future applications of radioactive Au NPs in oncology. Here, LDR Au NPs (103Pd:Pd@Au-PEG NPs) were injected in prostate cancer tumors. The particles were visualized at time-po...

Ultra-small superparamagnetic iron oxide nanoparticles (USPIOs) have been used as vascular contrast agents in magnetic resonance imaging (MRI), mainly for their capacity to generate negative contrast. To use USPIOs as positive contrast agents, it is necessary to achieve increased colloidal stability and signal-enhancement performance. Their molecular coatings must be carefully chosen so the vascular blood-pool contrast agents must lead to long blood turnover times. However, to avoid long-term toxicological effects, they must also be cleared rapidly through the urinary or the gastrointestinal pathways. In this context, highly stable USPIOs showing “positive” contrast in MRI and optimal clearance rates, call for the development of robust biocompatible molecular coatings. In the present study, USPIOs were stabilized with multidentate block copolymer (MDBC), using a one-pot polyol synthesis method in the presence of MDBC. Two types of MDBC having pendant COOH groups in the anchoring block were developed: a po...

When combined with 1H MRI, 19F MRI has the potential to combine high-resolution anatomical information with quantitative diagnostic. In this study, we report on the development of fluorinated mesoporous silica nanoparticles (MSNs), as dual 1H and 19F MRI probes. For this, MSNs were synthesised and covalently functionalized either with fluorosilane (FMSNs) or polyfluorosiloxane (polyFMSNs). Gadolinium chelates were also grafted on the particles, in order to confer 1H-MRI contrast enhancement to the imaging probes. Thus-treated nanoparticles were fully characterized and their 1H/19F relaxometric performances were thoroughly measured and compared. The 19F relaxation properties were found to be dependent on the concentration of fluorine; they were also highly sensitive to the presence of gadolinium. Better relaxivities were obtained with polyFMSNs, in comparison with those of FMSNs, leading to better 19F MRI sensitivity. Strong 1H relaxometric properties were also obtained for both nanoparticle systems, at la...

The fabrication of semiconductor products for the microelectronic industry requires the deposition of thin noble metal layers (e.g. Au-Sn and Pd) by means of processes involving fluid baths that contain metal ions (e.g. electrowinning and electroless plating). After several cycles, the plating solutions are used up and must be replaced, generating large volumes of discarded solutions containing precious metals. The metals (Au and Pd) are recovered either by electrowinning, a slow batch process, or by the use of toxic molecules (e.g. cyanides). This study demonstrates the possibility of using an atmospheric plasma technology to recover Au and Pd from these solutions, which provides a faster and greener process. Plasma discharges are generated at the surface of the solutions, causing ions to precipitate as nanoparticles. The treatment (few minutes only) allows the recovery of >95% gold, and >60% palladium. The process separates Au (NPs) from Sn ions (remaining in solution), as confirmed by elemental analysis and XPS. Particle size distributions of the nanoparticles recovered through the process suggests that as-synthesized nanoparticles could integrate value-added products (e.g. catalyst industry). Overall, the use of plasma technology could open several possibilities for the recycling of metals contained in solutions discarded from the semiconductor industry.

A single-step procedure for the preparation of Au–MnOx NPs was achieved through pulsed laser ablation of a gold–manganese metal target made of a pressed metal powder mixture. First, a 248 nm nanosecond laser at 66.7 J cm–2 was used to synthesize Au–MnOx NPs from a gold–manganese metal target immersed in an aqueous solution at pH 11 (NaOH). It is demonstrated that the Au–MnOx NPs are made of a small Au core (around 5 nm in diameter) surrounded by a very thin manganese oxide layer (0.3–1.3 nm) as characterized by TEM, HAADF HR-STEM, and EELS. The superficial MnOx layer has a local structure that bears a close resemblance to that of Mn2O3 and MnO2 as revealed by EXAFS and XANES measurements. Comparative studies were also performed with a 1064 nm nanosecond laser at 1.4 J cm–2. In that case, the resulting colloids are mainly made of a mixture of Au NPs and MnOx NPs, with few Au–MnOx NPs, thereby suggesting the impact of the laser wavelength and fluence on the synthesis process. The mechanisms responsible for ...

An effective mussel-inspired multidentate block copolymer strategy having pendant anchoring catechol groups (Cat-MDBC) to stabilize extremely small iron oxide nanoparticles (ESNPs) in water is reported. The resultant aqueous Cat-MDBC/ESNP colloids with diameter ≈16 nm and core diameter ≈2 nm were non-toxic to cells up to 200 μg/mL and exhibit excellent colloidal stability in physiological condition (pH=7) as well as in the presence of IgG model protein. More promisingly, they had the relaxivity ratio to be r2/r1=1.5, which is significantly lower than PEG-coated SNPs with core diameter=1.5-6 nm; further which is similar to those of Gd-DOTA T1-weighted contrast agents. These results suggest that aqueous Cat-MDBC/ESNP colloids could be a promising candidate for T1-weighted MRI contrast enhancement.

Mesoporous silica nanoparticles (MSNs) are considered as one of the most promising nanovectors for controlled drug delivery. For the design of ideal drug nanocarriers, several factors have to be taken into account, such as size and surface chemistry. Here, we report how MSNs surface functionalization and particle size critically affect the drug release performances and therapeutic capabilities. We illustrate the size effect of these functionalized MSNs on in vitro, intracellular, and in vivo drug release efficiency, as well as on nanoparticle and drug diffusion into the targeted tissues (tumor). For this, dispersible MSNs with different particle sizes (from 500 down to 45 nm), similar physicochemical properties (e.g., structural and textural properties), and high colloidal stability (even in saline conditions), were synthesized. Their surface was specifically functionalized with a phosphonate-silane according to a novel postgrafting strategy, for better control over loading and release of positively charg...

Rivka Galchen’s novel Atmospheric Disturbances employs what James Wood calls “triple unreliability” to interrogate the ability/inability of the human mind to engage in a purely objective, rational experience of being in the world. Taking Wood’s interpretation of the novel beyond narrative structure itself, this article argues that Galchen’s intertwining of meteorological and psychological theories produces a text that asks readers to question the very idea of narrative possibility, their personal beliefs, and literature as a form of “truth” about any epistemological understanding of human relations with the external world. Whereas the narrator’s reliability is undermined in the novel in order to interrogate the nature of loss, love, belief, and perception, so too does the novel form a relationship between reader and text that undermines the possibility of literary interpretation and the “real” psychological state of the narrator. In looking at how Galchen’s novel combines meteorological principles, the Doppler effect, interpretive error, and completion error, this article argues that if the reader chooses to assume that the narrator’s construction of reality is flawed, then he or she is only doing so because of the desire to judge the fictionality of the text by his/her consensus view of reality. The narrator’s reality is the only reality the reader can ever know, and, in this particular text, such an interpretation would be based upon attempts at what the text suggests is a completion error based on individual experience—including, most importantly, the individual experience of the reader. In the case of Galchen’s work, this “completion” runs counter to an objective interpretation of the genre of the text. The novel effectively provides a single-Doppler interpretation of events that allows for a critique of interpretation as fundamentally stemming from belief, and, more importantly, from the reader’s own interpretive strategies founded on his or her individual belief about what “truth” signifies within the fictional world of the novel.

International audience; In this manuscript, we present a new strategy for the direct synthesis of functional nano-composite hybrid therapeutic vectors. The smart coupling of soft-chemistry and “ouzo effect” based emulsification processing allows us to create in a very simple way a Pickering stabilized emulsion from various prodrug modelling molecules used as a core, and subsequently embedded into a mesostructured silica shell. The resulting prodrug/Fe2O3/silica architecture offers a very good functionality/complexity ratio, realistic from a pharmaceutical development point of view at the industrial scale. While usual magnetic resonance imaging (MRI) contrast agent properties of maghemite nanoparticles are maintained, we proved for the first time that their smart localization at the organic/silica interface allows us to isolate them from phosphate anions of the surrounding environment, and thus to use their surface as a heterogeneous catalyst for controlled hydrolysis-mediated model drug delivery. This original hydrolysis-mediated release mechanism was investigated by grafting a model drug molecule via various covalent bonds. The release time can be tuned by this approach in between one hour and three days. In addition, magnetic radio frequency stimulation commonly used for hyperthermia treatment was able to accelerate the catalytic hydrolysis and release of the model drug by one order of magnitude, proving that drug release can be triggered on demand.

Colloidal ultrasmall superparamagnetic iron oxide nanoparticles (USNPs) with better control of their surface chemistry have been considered as a biocompatible alternative to clinically used gadolinium-based contrast agents for in vivo bright magnetic resonance imaging (MRI). Herein, we report a versatile mussel-inspired multidentate block copolymer strategy that allows for the stabilization of USNPs as promising MRI contrast agents with excellent colloidal stability. A well-controlled multidentate block copolymer with pendant multiple catechol groups (Cat-MDBC) is synthesized by a combination of controlled radical polymerization and postmodification methods. The Cat-MDBC proves to be effective to strongly anchor to USNP surfaces as well as provide optimal hydrophilic surfaces, thus enabling the fabrication of aqueous Cat-MDBC/USNP colloids at single layers with a diameter of ≈20 nm through a biphasic ligand exchange process. They exhibit excellent colloidal stability in broad pH range and physiological co...

Alginate-based hydrogels are widely used for the development of biomedical scaffolds in regenerative medicine. The use of sugar glass as a sacrificial template for fluidic channels fabrication within alginate scaffolds remains a challenge because of the premature dissolution of sugar by the water contained in the alginate as well as the relatively slow internal gelation rate of the alginate. Here, a new and simple method, based on a sugar glass fugitive ink loaded with calcium chloride to build sacrificial molds, is presented. We used a dual calcium cross-linking process by adding this highly soluble calcium source in the printed sugar, thus allowing the rapid gelation of a thin membrane of alginate around the sugar construct, followed by the addition of calcium carbonate and gluconic acid δ-lactone to complete the process. This innovative technique results in the rapid formation of ''on-demand'' alginate hydrogel with complex fluidic channels that could be used in biomedical applications such as highly vascularized scaffolds promoting pathways for nutrients and oxygen to the cells.

Gold nanoparticles have properties useful in biomedical imaging and cancer therapy. This biocompatible metal has been used for centuries in medicine. In the last 20 years, the rapid developments in nanotechnology have revealed several applications of nanosized gold, which are now being evaluated for clinical procedures. For instance, gold nanoparticles can be used to develop sensors due to their optical properties; they also make possible the development of new hyperthermia and drug delivery treatments. However, gold nanoparticles could find more immediate and direct applications in medical physics procedures, such as X-ray imaging and radiotherapy. First, this chapter provides an overview of the different synthesis routes for the production of biomedical gold nanoparticles. Then, an overview of the physical principles of photon–matter interactions, that are fundamental to the concept of X-ray attenuation in biological tissues, is presented. The properties of gold nanoparticles as contrast agents for X-ray and computed tomography (CT) imaging are reviewed, along with the principles of the radiosensitization effect useful in medical physics and oncology. The main mechanisms leading to dose enhancement, to cell damage and to cell death, are described in the light of the specific interactions taking place between ionizing photons and high-Z materials such as gold (Au) when these are distributed in biological tissues such as tumours. Finally, the performance of gold nanoparticles as CT contrast agents and radiosensitizers in oncology is discussed, in the perspective of their consideration for clinical applications.

Mesoporous silica nanoparticles (MSNs) are being developed as drug delivery vectors. Biomedical imaging (MRI and PET) enables their tracking in vivo, provided their surface is adequately grafted with imaging probes (metal chelates). However, MSNs are characterized by huge specific surfaces, and high-quality metal chelate anchoring procedures must be developed and validated, to demonstrate that their detection in vivo is associated to the presence of nanoparticles and not to detached metal chelates. MCM-48 nanospheres (M48SNs, 150 nm diam., 3-D pore geometry) were synthesized and functionalized with diethylenetriaminepentaacetic acid (DTPA). The strong grafting of DTPA was confirmed by 29Si MAS-NMR, XPS, FTIR and TGA. The particles were labeled with paramagnetic ions Gd3+ (for MRI) as well as radioactive ions 64Cu2+ (for PET; half-life: 12.7 h). Gd3+-DTPA-M48SNs formed a stable colloid in saline media for at least 6 months, without any sign of aggregation. The relaxometric properties were measured at various magnetic fields. The strength of DTPA binding at the surface of MSNs was also assessed in vivo, by injecting mice (i.v.) with Gd3+/64Cu2+-DTPA-M48SNs. Vascular retention and urinary clearance were monitored by MRI, whereas the PET modality provided dynamic and quantitative assessment of biodistribution and blood/organ clearance. No significant 64Cu activity was detectable in the bladder. The study confirmed the very limited detachment of DTPA from M48SNs cores once injected in vivo. The transit of MSNs through the liver and intestinal tract, does not lead to evidence of Gd3+/64Cu2+-DTPA in the urine. This physico-chemical and biodistribution study confirms the quality of DTPA attachment at the surface of the particles, necessary to allow further development of PET/MRI-assisted MSN-vectorized drug delivery procedures.

The radioisotope palladium (103Pd), encapsulated in millimetre-size seed implants, is widely used in prostate cancer brachytherapy. Gold nanoparticles (Au NPs) distributed in the vicinity of 103Pd radioactive implants, strongly enhance the therapeutic dose of radioactive implants (radiosensitisation effect). A new strategy under development to replace millimetre-size implants, consist in injecting radioactive NPs in the affected tissues. The development of 103Pd@Au NPs distributed in the diseased tissue, could increase the uniformity of treatment (compared with massive seeds), while enhancing the radiotherapeutic dose to the cancer cells (through Au-mediated radiosensitisation effect). To achieve this goal, it is necessary to develop a rapid, efficient, one-pot and easy-to-automatise procedure, allowing the synthesis of core-shell Pd@Au NPs. The novel synthesis route proposed here enables the production of Pd@Au NPs in not more than 4 h, in aqueous media, with minimal manipulations, and relying on biocompatible and non-toxic molecules. This rapid multi-step process consists of the preparation of ultra-small Pd NPs by chemical reduction of an aqueous solution of H2PdCl4 supplemented with ascorbic acid (AA) as reducing agent and 2,3-meso-dimercaptosuccinic acid (DMSA) as a capping agent. Pd conversion yields close to 87% were found, indicating the efficiency of the reaction process. Then Pd NPs were used as seeds for the growth of a gold shell (Pd@Au), followed by grafting with polyethylene glycol (PEG) to ensure colloidal stability. Pd@Au-PEG (TEM: 20.2 ± 12.1 nm) formed very stable colloids in saline solution as well as in cell culture medium. The physico-chemical properties of the particles were characterised by FTIR, XPS, and UV-vis. spectroscopies. The viability of PC3 human prostate cancer cells was not affected after a 24 h incubation cycle with Pd@Au-PEG NPs to concentrations up to 4.22 mM Au. Finally, suspensions of Pd@Au-PEG NPs measured in computed tomography (CT) are found to attenuate X-rays more efficiently than commercial Au NPs CT contrast media. A proof-of-concept was performed to demonstrate the possibility synthesise radioactive 103Pd:Pd@Au-PEG NPs. This study reveals the possibility to synthesise Pd@Au NPs rapidly (including radioactive 103Pd:Pd@Au-PEG NPs), and following a methodology that respects all the strict requirements underlying the production of NPs for radiotherapeutic use (rapidity, reaction yield, colloidal stability, NPs concentration, purification).

Nanocrystals of Zn(Fe)O-based diluted magnetic semi-conductor (nanoDMS) have been prepared by forced hydrolysis in polyol medium, using zinc and iron salts, and coated with carboxymethylpullulan (CMP). TEM studies revealed that CMP-nanoDMS are spherical, with average diameters on the order of 20 nm. Hydrodynamic diameters of about 75 nm were found in a physiological medium. NanoDMS were superparamagnetic at body temperature, and exhibited high saturation magnetization values (3.25 emu g−1). In aqueous suspensions, the colloids revealed high transverse proton relaxivities (T2) with an r2 value of 203 mM−1 s−1 (300 K, 1.41 T). Visible photoluminescent properties were evidenced with an excitation wavelength of 366 nm. No evidence of cell toxicity was found for human endothelial cells incubated with CMP-nanoDMS, at concentrations up to 100 μg mL−1 and for 48 h. No modification to the cytoskeleton was found up to 6 days of exposure. These hybrid nanomaterials could be considered as novel potential MR and luminescent bioimaging agents.

Mesoporous silica nanoparticles (MSNs) have emerged as promising bio- materials for drug delivery and cell tracking applications, for which MRI is the medical imaging modality of choice. In this contribution, MRI contrast agents (DTPA-Gd) and polyethylene glycol (PEG) are grafted selectively at the surface of MSNs, in order to achieve optimal relaxometric and drug loading performances. In fact, DTPA and PEG grafting procedures reported until now, have resulted in signifi cant pore obstruction, which is detrimental to the drug delivery function of MSNs. This usually induces a dramatic decrease in surface area and pore volume, thus limiting drug loading capacity. Therefore, these molecules must be selectively grafted at the outer surface of MSNs. In this study, 3D pore network MSNs (MCM-48-type) are synthesized and func- tionalized with a straightforward and effi cient grafting procedure in which DTPA and PEG are selectively grafted at the outer surface of MSNs. No pore blocking is observed, and more than 90% of surface area, pore volume and pore diameter are retained. The thus-treated particles are colloidally stable in SBF and cell culture media, they are not cytotoxic and they have high drug loading capacity. Upon labeling with Gd, the nanoparticle suspensions have strong relaxometric properties (r 2 /r 1 = 1.47, r 1 = 23.97 mM −1 s −1 ), which con- fers a remarkable positive contrast enhancement potential to the compound. The particles could serve as effi cient drug carriers, as demonstrated with a model of daunorubicin submitted to physiological conditions. The selective nanoparticle surface grafting procedures described in the present article represent a signifi cant advance in the design of high colloidal stability silica- based vectors with high drug loading capacity, which could provide novel theranostic nanocompounds.

Magnetic resonance imaging (MRI) has developed at an exponential rate over the last decades, and the development of contrast agents to enhance the visualization of organs has followed the same trend. Meanwhile, magnetic nanoparticles that generate either “positive” or “negative” contrast in MRI have become one of the most important biomedical applications of nanotechnology. Indeed, superparamagnetic iron oxide nanoparticles, as negative contrast agents for T 2/T 2 * -weighted imaging, have found numerous applications in preclinical and clinical MRI (cell labeling, vascular contrast, lymph node imaging, liver contrast). In addition to this, paramagnetic and antiferromagnetic nanoparticles based on the elements Gd3+ and Mn2+ have mainly been exploited in vascular procedures and targeted imaging, for their capacity to enhance the MR signal of blood and of molecular signatures of endovascular disease. They are commonly referred to as “positive” contrast agents for T 1-weighted imaging.

Drug delivery at the nano-scale is becoming an important topic in nano and regenerative medicine as it can offer a very localized therapy. Therefore, niosomes are one of the most important vehicles to release drug at the nanoscale. In this paper, we present a new automated microsystem for niosome generation on-demand. Used niosome were based on a mixture of cholesterol and dicetyl phosphate with chloroform. Three compact micropumps are connected to a microfluidic substrate in order to generate 100 nm noisome vesicles. Through this paper we also investigated the impact of using 150 μm pseudo-Y and cross shape microchannel on the diameter of vesicles. We have observed reliable results with Y-shaped microchannel, which was able to generate vesicles down to 91 nm. All the system is based on a low-cost fabrication process using dry photo resist.

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an “intelligent” drug delivery system based on a feedback loop to monitor drug delivery.

In recent years, pulsed laser ablation in liquids (PLAL) has emerged as a new green chemistry method to produce different types of nanoparticles (NPs). It does not require the use of reducing or stabilizing agents, therefore enabling the synthesis of NPs with highly-pure surfaces. In this study, pure Au NPs were produced by PLAL in aqueous solutions, sterically stabilized using minimal PEG excess, and functionalized with manganese chelates to produce a dual CT/MRI contrast agent. The small hydrodynamic size (36.5 nm), low polydispersity (0.2) and colloidal stability of Au NPs@PEG-Mn2+ were demonstrated by DLS. The particles were further characterized by TEM, XPS, FTIR and 1H NMR to confirm the purity of the Au surfaces (i.e. free from the common residual chemicals found after NP synthesis) and the presence of the different surface molecules. The potential of these particles as contrast agents for CT/MRI was assessed in vivo (e.g. chicken embryo). Au NPs@PEG-Mn2+ also demonstrated strong blood retention for at least 90 minutes following intravenous injection in mouse models. The promising performance of PEGylated PLAL-synthesized Au NPs containing manganese chelates could open new possibilities for the production of purer dual imaging contrast agents based on Au colloids.

International audience; Persistent luminescence and magnetic properties of Gd2O2S: Eu 3+ , Ti 4+ , Mg 2+ nanoparticles have been studied to attest the relevance of such nanoparticles as nanoprobes for multimodal imaging. The development of new imaging tools is required to improve the quality of medical images and then to diagnose some disorders as quickly as possible in order to ensure more effective treatment. Multimodal imaging agents here developed combine the high resolution abilities of Magnetic Resonance Imaging (MRI) with another more sensitive technique, like optical imaging, leading significant possibilities for early detection of diseases and a better understanding of pathologies. Recently, inorganic persistent luminescent nanoparticles (i-PLNPs) have been reported as suitable probes for in vivo imaging that meet the difficulties due to the biological environment. The i-PLNPs are first excited by a UV light for a few minutes outside the animal before injection and emit in the border of the red/NIR window for hours after the injection. In this paper, we explore a new chemical composition of host lattice doped with transition metal and lanthanide ions for persistent luminescence that contains a paramagnetic centre conferring additional magnetic properties for a use in MRI, and that can be obtained at the nanoscale. Thus, advanced Gd2O2S nanoparticles exhibiting both persistent luminescence and paramagnetic properties have been synthesized and fully characterized. Their luminescent properties were determined as well as their magnetic properties. One compound sample with composition Gd2O2S: Eu 3+ (5%), Ti 4+ (1%), Mg 2+ (8%) presents both optical and magnetic properties suitable for a bimodal imaging probe. Indeed, it shows an afterglow in the red range at 620 nm and a relaxivity corresponding to r2 / r1 ratio of 1.28.

Ultrasmall paramagnetic Gd(2)O(3) nanoparticles have been developed as contrast agents for molecular and cellular preclinical MRI procedures. These small particles (mean diameter

Thin films made of mesoporous silica nanoparticles (MSNs) are finding new applications in catalysis, optics, as well as in biomedicine. The fabrication of MSNs thin films requires a precise control over the deposition and sintering of MSNs on flat substrates. In this study, MSNs of narrow size distribution (150 nm) are synthesized, and then assembled onto flat silicon substrates, by means of a dip-coating process. Using concentrated MSN colloidal solutions (19.5 mg mL(-1) SiO2), withdrawal speed of 0.01 mm s(-1), and well-controlled atmospheric conditions (ambient temperature, ∼ 70% of relative humidity), monolayers are assembled under well-structured compact patterns. The thin films are sintered up to 900 °C, and the evolution of the MSNs size distributions are compared to those of their pore volumes and densities. Particle size distributions of the sintered thin films were precisely fitted using a model specifically developed for asymmetric particle size distributions. With increasing temperature, there is first evidence of intraparticle reorganization/relaxation followed by intraparticle sintering followed by interparticle sintering. This study is the first to quantify the impact of sintering on MSNs assembled as thin films.

Mesoporous silica nanoparticles (MSNs) are of growing interest for the development of novel probes enabling efficient tracking of cells in vivo using magnetic resonance imaging (MRI). The incorporation of Gd3+ paramagnetic ions into highly porous MSNs is a powerful strategy to synthesize “positive” MRI contrast agents for more quantitative T1-weighted MR imaging. Within this context, different strategies have been reported to integrate Gd chelates to 2D pore network MSNs. As an alternative, we report on the modulation of the pore network topology through the preparation of a 3D pore network hybrid GdSixOy MSN system. In this study, 2D GdSixOy-MSNs with similar porosity and particle size were also prepared and the relaxometric performances of both materials, directly compared. Both syntheses lead to water-dispersible MSNs suspensions (particle size < 200 nm), which were stable for at least 48h. 3D GdSixOy-MSNs provided a significant increase in 1H longitudinal relaxivity (18.5 s−1mM−1; 4.6 times higher than Gd-DTPA) and low r2/r1 ratios (1.56) compatible with the requirements of “positive” contrast agents for MRI. These results demonstrate the superiority of a 3D pore network to host paramagnetic atoms for MRI signal enhancement using T1-weighted imaging. Such an approach minimizes the total amount of paramagnetic element per particle.

Over the last few decades, gold nanoparticles (GNPs) have emerged as "radiosensitizers" in oncology. Radiosensitizers are additives that can enhance the effects of radiation on biological tissues treated with radiotherapy. The interaction of photons with GNPs leads to the emission of low-energy and short-range secondary electrons, which in turn increase the dose deposited in tissues. In this context, GNPs are the subject of intensive theoretical and experimental studies aiming at optimizing the parameters leading to greater dose enhancement and highest therapeutic effect. This review describes the main mechanisms occurring between photons and GNPs that lead to dose enhancement. The outcome of theoretical simulations of the interactions between GNPs and photons is presented. Finally, the findings of the most recent in vivo studies about interactions between GNPs and photon sources (e.g., external beams, brachytherapy sources, and molecules labeled with radioisotopes) are described. The advantages and challenges inherent to each of these approaches are discussed. Future directions, providing new guidelines for the successful translation of GNPs into clinical applications, are also highlighted.