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With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy., We report the successful use of a gastro-resistant covalent organic framework for in vivo oral delivery of insulin.

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.

Triphenylphosphine (TPP) surface-functionalized and F-108 Pluronic-stabilized gold nanoparticles (F-108@TPP-AuNPs) have been synthesized through a one-step approach, leading to well-defined (9.6±1.6 nm) and water-soluble nanoparticles by microwave heating an aqueous solution of TPP-AuI Cl in the presence of a Pluronic polymer under basic conditions. TPP release was negligible under physiological conditions, but enhanced significantly at an acidic pH (5.4) mimicking that of a cancer cell. Laser irradiation (532 nm) raised the temperature of an aqueous solution of F-108@TPP-AuNPs to 51.7 °C within 5 min, confirming efficient light-to-heat conversion capabilities without significant photodegradation. TEM confirmed intracellular localization of F-108@TPP-AuNPs in the cytosol, endosomes and lysosomes of HeLa cells. F-108@TPP-AuNPs were well tolerated by HeLa cells and zebrafish embryos at ambient temperatures and became toxic upon heat activation, suggesting synergistic interactions between heat and cytotoxic action by TPP.

International audience; Two calix[4]arene systems, C234+ and C244+, where 2 corresponds to the number of viologen units and 3-4 corresponds to the number of carbon atoms connecting the viologen units to the macrocyclic core, have been synthesized and led to the formation of [3]pseudorotaxanes when combined with either CB[7] or CB[8]. The [3]pseudorotaxanes spontaneously dissociate upon reduction of the bipyridinium units as the result of intramolecular dimerization of the two face-to-face viologen radical cations. CB[7] and CB[8]-based [2]pseudorotaxanes containing monomeric viologen guest models compounds, MC32+ and MC4+, do not undergo decomplexation and dimerization following electrochemical reduction of their bipyridinium units.

Hollow particles have been extensively used in bioanalytical and biomedical applications for almost two decades due to their unique and tunable optoelectronic properties as well as their significantly high loading capacities. These intrinsic properties led them to be used in various bioimaging applications as contrast agents, controlled delivery (i.e. drugs, nucleic acids and other biomolecules) platforms and photon-triggered therapies (e.g. photothermal and photodynamic therapies). Since recent studies showed that imaging-guided targeted therapeutics have higher success rates, multimodal theranostic platforms (combination of one or more therapy and diagnosis modality) have been employed more often and hollow particles (i.e. nanoshells) have been one of the most efficient candidates to be used in multiple-purpose platforms, owing to their intrinsic properties that enable synergistic multimodal performance. In this review, recent advances in the applications of such hollow particles fabricated with various routes (either inorganic or organic based) were summarized to delineate strategies for tuning their properties for more efficient biomedical performance by overcoming common biological barriers. This review will pave the ways for expedited progress in design of next generation of hollow particles for clinical applications.

A set of metal–organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells––including those resistant to cisplatin––and in zebrafish embryos. In cultured cells, M-TKs generated reactive oxygen species that triggered apoptosis via the mitochondrial pathway without directly disrupting the cell-membrane or damaging nuclear DNA. The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal–organic knots as a new field of chemical space for pharmaceutical design and development.

Iron oxide (γ-Fe2O3) nanoparticles (NPs) were efficiently coated with the water soluble macrocycle cucurbit[7]uril (CB[7]) by microwave heating. Density functional theory (DFT) calculations support a binding model in which the carbonyl oxygens of CB[7] coordinate directly to surface Fe3+ ions. The modified particles (CB[7]NPs) are stable under a wide pH range (2–12) and have a transverse relaxivity, R2, of 113 s−1 mM−1. Nile red (NR) dye was loaded into the cavities of the surface-adsorbed CB[7]s, and intracellular delivery of the dye to HCT116 cells was observed by confocal laser scanning microscopy. The dye-loaded particles (CB[7]NPs⊃NR) have a R2 of 172 s−1 mM−1. The stability, biocompatibility, and dual purpose functionality (drug delivery and magnetic resonance imaging) of the CB[7]NPs herald the theranostic potential of this system.

We present the synthesis of a silver nanoparticle (AgNP) based drug-delivery system that achieves the simultaneous intracellular delivery of doxorubicin (Dox) and alendronate (Ald) and improves the anticancer therapeutic indices of both drugs. Water, under microwave irradiation, was used as the sole reducing agent in the size-controlled, bisphosphonate-mediated synthesis of stabilized AgNPs. AgNPs were coated with the bisphosphonate Ald, which templated nanoparticle formation and served as a site for drug attachment. The unreacted primary ammonium group of Ald remained free and was subsequently functionalized with either Rhodamine B (RhB), through amide formation, or Dox, through imine formation. The RhB-conjugated NPs (RhB–Ald@AgNPs) were studied in HeLa cell culture. Experiments involving the selective inhibition of cell membrane receptors were monitored by confocal fluorescence microscopy and established that macropinocytosis and clathrin-mediated endocytosis were the main mechanisms of cellular uptake. The imine linker of the Dox-modified nanoparticles (Dox–Ald@AgNPs) was exploited for acid-mediated intracellular release of Dox. We found that Dox–Ald@AgNPs had significantly greater anti-cancer activity in vitro than either Ald or Dox alone. Ald@AgNPs can accommodate the attachment of other drugs as well as targeting agents and therefore constitute a general platform for drug delivery.

Drug-loaded magnetic nanoparticles were synthesized and used for the sequential delivery of the antiresorptive agent zoledronic acid (Zol) and the cytotoxic drug doxorubicin (Dox) to breast cancer cells (MCF-7). Zol was attached to bare iron oxide nanoparticles (IONPs) via phosphonate coordination to form Z-NPs. The unbound imidazole of Zol was then used to complex the organic macrocycle CB[7] to obtain CZ-NPs. Dox was complexed to the CZ-NPs to form the fully loaded particles (DCZ-NPs), which were stable in solution at 37 °C and physiological pH (7.4). Fluorescence spectroscopy established that Dox is released in solution from DCZ-NPs suddenly (i) when the particles are subjected to magnetically induced heating to 42 °C at low pH (5.0) and (ii) in the presence of glutathione (GSH). Mass spectrometry indicated that Zol is released slowly in solution at low pH after Dox release. Magnetic measurements with a magnetic reader revealed that DCZ-NPs are internalized preferentially by MCF-7 cells versus nonmalignant cells (HEK293). Zol and Dox acted synergistically when delivered by the particles. DCZ-NPs caused a decrease in the viability of MCF-7 cells that was greater than the net decrease caused when the drugs were added to the cells individually at concentrations equivalent to those delivered by the particles. MCF-7 cells were treated with DCZ-NPs and subjected to an alternating magnetic field (AMF) which, with the nanoparticles present, raised the temperature of the cells and triggered the intracellular release of Dox, as indicated by fluorescence activated cell sorting (FACS). The cytotoxic effects of the DCZ-NPs on MCF-7 cells were enhanced 10-fold by AMF-induced heating. DCZ-NPs were also able to completely inhibit MCF-7 cell adhesion and invasion in vitro, indicating the potential of the particles to act as antimetastatic agents. Together these results demonstrate that DCZ-NPs warrant development as a system for combined chemo- and thermo-therapeutic treatment of cancer.

[Abstract] Cucurbit[7]uril-modified iron-oxide nanoparticles (CB[7]NPs) were loaded with doxorubicin hydrochloride (Dox) and tested as a drug delivery system. Dox was found to interact with the carbonyl-rich rims of the CB[7] macrocycles adsorbed on the surface of the nanoparticles. The Dox-loaded nanoparticles (Dox@CB[7]NPs) were stable at room temperature and physiological pH and released their Dox cargo under acidic conditions, in the presence of glutathione, or with heating. Dox@CB[7]NPs reduced the viability of HeLa and three other cancer-derived cell lines in vitro at lower IC50 than free Dox. They were also nontoxic to C. elegans. The sensitivity of HeLa cells to Dox@CB[7]NPs was enhanced when the temperature was elevated by application of an alternating magnetic field. Thus, Dox@CB[7]NPs show promise as agents for the intracellular delivery of Dox to cancer cells, for the selective and controlled release of the drug, and, more generally, as a possible means of combining chemotherapeutic and hyperthermic treatment modalities. Al Jalila Foundation; AJF 201425 Al Jalila Foundation; AJF 201538

A host–guest complex of 6-mercaptonicotinic acid (MNA) and cucurbit[7]uril (CB7) was prepared and conjugated to γ-Fe3O4 nanoparticles (NPs) to detect toxic cadmium ions in water as a solid-state sensor. The formation of an inclusion host–guest complex with CB7 was confirmed by UV–vis absorption and proton NMR spectroscopy. CB7 preferentially binds the protonated MNA form compared to the neutral form, demonstrated by a binding constant for the protonated form that is four orders of magnitude higher than that of the neutral form. An increase in the pKa of MNA by 1.2 units was demonstrated after the addition of CB7, which further supports preferential binding between MNA and CB7. The NMR results confirm binding to cadmium via the carboxylic acid moiety. Stationary and time-resolved fluorescence results, in solution and in the solid state, indicate that cadmium and CB7 cause a blue shift in the MNA emission bands and extend its excited-state lifetime due to dissociation of the MNA dimer. In the solid state, switching the emission signals between Cd2+-MNA/CB7NPs (ON state) and MNAH+/CB7NPs (OFF state) was achieved by controlling the pH. An efficient, regenerable, and stable sensor device was fabricated for sensitive and selective detection of Cd2+ in contaminated water samples.

A set of metal–organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells––including those resistant to cisplatin––and in zebrafish embryos., A set of metal–organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells––including those resistant to cisplatin––and in zebrafish embryos. In cultured cells, M-TKs generated reactive oxygen species that triggered apoptosis via the mitochondrial pathway without directly disrupting the cell-membrane or damaging nuclear DNA. The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal–organic knots as a new field of chemical space for pharmaceutical design and development.

Mesoporous iron-oxide nanoparticles (mNPs) were prepared by using a modified nanocasting approach with mesoporous carbon as a hard template. mNPs were first loaded with doxorubicin (Dox), an anticancer drug, and then coated with the thermosensitive polymer Pluronic F108 to prevent the leakage of Dox molecules from the pores that would otherwise occur under physiological conditions. The Dox-loaded, Pluronic F108-coated system (Dox@F108-mNPs) was stable at room temperature and physiological pH and released its Dox cargo slowly under acidic conditions or in a sudden burst with magnetic heating. No significant toxicity was observed in vitro when Dox@F108-mNPs were incubated with noncancerous cells, a result consistent with the minimal internalization of the particles that occurs with normal cells. On the other hand, the drug-loaded particles significantly reduced the viability of cervical cancer cells (HeLa, IC50 =0.70 μm), wild-type ovarian cancer cells (A2780, IC50 =0.50 μm) and Dox-resistant ovarian cancer cells (A2780/AD, IC50 =0.53 μm). In addition, the treatment of HeLa cells with both Dox@F108-mNPs and subsequent alternating magnetic-field-induced hyperthermia was significantly more effective at reducing cell viability than either Dox or Dox@F108-mNP treatment alone. Thus, Dox@F108-mNPs constitute a novel soft/hard hybrid nanocarrier system that is highly stable under physiological conditions, temperature-responsive, and has chemo- and thermotherapeutic modes of action.

Cucurbit[7]uril modified iron oxide nanoparticles (CB[7]NPs) were loaded with palladium to form nano-catalysts (Pd@CB[7]NPs) that, with microwave heating, catalysed Suzuki-Miyaura, Sonogashira, and Mizoroki-Heck cross-coupling reactions. Reactions were run in environmentally benign 1:1 ethanol/water solvent under convenient aerobic conditions. In a preliminary screening, conversions and yields were uniformly high with turn over frequencies (TOF) ranging from 64 to 7360 h-1 . The nano-catalysts could be recovered with a magnet and reused several times (6 times for Suzuki-Miayura reaction) without loss of activity.

Covalent organic nanosheets (CONs) have attracted much attention because of their excellent physical, chemical, electronic, and optical properties. Although covalent organic nanosheets have widely been used in many applications, there are only a few CONs that have been tested for bio-medical applications. Nanometer sized triazine-based nanosheets were obtained by exfoliating their bulk counterparts in water. The obtained nanosheets were dispersible and stable in water with enhanced photoluminescence properties compared to the bulk material. The nanosheets were biocompatible and non-toxic and showed ability to stain HeLa cell nuclei without additional assistance of an external targeting agent.

Non-toxic covalent organic nanosheet-based fluorescent nuclear stains., Covalent organic nanosheets (CONs) have attracted much attention because of their excellent physical, chemical, electronic, and optical properties. Although covalent organic nanosheets have widely been used in many applications, there are only a few CONs that have been tested for bio-medical applications. Nanometer sized triazine-based nanosheets were obtained by exfoliating their bulk counterparts in water. The obtained nanosheets were dispersible and stable in water with enhanced photoluminescence properties compared to the bulk material. The nanosheets were biocompatible and non-toxic and showed ability to stain HeLa cell nuclei without additional assistance of an external targeting agent.

International audience; Magnetic and fluorescent assemblies of iron-oxide nanoparticles (NPs) were constructed by threading a viologen-based ditopic ligand, DPV2+, into the cavity of cucurbituril (CB[7]) macrocycles adsorbed on the surface of the NPs. Evidence for the formation of 1:2 inclusion complexes that involve DPV2+ and two CB[7] macrocycles was first obtained in solution by 1H NMR and emission spectroscopy. DPV2+ was found to induce self-assembly of nanoparticle arrays (DPV2+⊂CB[7]NPs) by bridging CB[7] molecules on different NPs. The resulting viologen-crosslinked iron-oxide nanoparticles exhibited increased saturation magnetization and emission properties. This facile supramolecular approach to NP self-assembly provides a platform for the synthesis of smart and innovative materials that can achieve a high degree of functionality and complexity and that are needed for a wide range of applications.

Biochars from two different biomass (rhodes grass and fronds of date palm) were produced using the same pyrolysis condition (1 atm, 400 °C, heating rate of 5 °C min −1 , duration of 11 h) and compared in terms of chemical composition, thermal stability, and respective microstructures. Proximate analysis of the biochars showed rhodes grass has higher fixed carbon (56.6 wt%), lower volatile (11.8 wt%) and higher ash (28.8 wt%) compared to date palm biochar (fixed carbon 45 wt%; volatile 43.2 wt%; ash 7.1 wt%). The pH of the two biochars were similar (∼9.6). Elemental analysis showed that carbon becomes enriched, whereas hydrogen, oxygen and sulfur become depleted after pyrolysis. The elemental O/C and (O + N)/C ratios are lower in rhodes grass biochar (0.11 and 0.12 respectively) compared to date palm biochar (0.32 and 0.33 respectively), but both biochars have a similar H/C ratio (0.46 for rhodes grass and 0.49 for date palm). Thermogravimetric Analysis (TGA) performed in inert gas (N 2 ) showed considerable differences in the thermal degradation profile of the two biochars. Only one degradation event occurring over a wide temperature range (120–1000 °C; no obvious degradation maximum) was observed in rhodes grass, whereas two degradation events were observed in date palm – the first occurring rapidly (280–380 °C; maximum at 340 °C) and the second event occurring slowly over a wider temperature range (380–1000 °C; no temperature maximum detected). The Fourier transform infrared (FTIR) spectra of both biochars are featureless in comparison to raw biomass, but bands assigned to O–H stretching (3200–3000 cm −1 ) and C–H stretching (3100–3000 cm −1 ) while markedly decreased suggest cellulose might not have been completely decomposed during pyrolysis. The BET surface area of rhodes grass biochar is higher (16.78 m 2 g −1 ) compared to date palm biochar (1.99 m 2 g −1 ). This is in agreement with scanning electron microscopy investigations (SEM) which show that the average pore size diameter is smaller in rhodes grass biochar (3.1 μm + 0.3 μm) compared to the one of date palm biochar (7.2 μm ± 2.9 μm). Changes in the distribution of pore size diameter in the two biomass before and after pyrolysis suggests date palm is relatively heat sensitive in comparison to rhodes grass. Overall, our results demonstrate that both biochars are substantially different despite being produced under the same pyrolysis condition.

Paul Ehrlich's vision of a "magic bullet" cure for disease inspires the modern design of nanocarriers whose purpose is to deliver drug cargo to specific sites in the body while circumventing endogenous immunological clearance mechanisms. Iron oxide nanoparticles (IONPs) have emerged as particularly promising nanocarriers because of their biodegradability, ability to be guided magnetically to sites of pathology, mediation of hyperthermic therapy, and imaging capabilities. In this review, we focus on the design and drug-delivery aspects of IONPs coated with organic macrocycles (crown ethers, cyclodextrins, calix[n]arenes, cucurbit[n]urils, or pillar[n]arenes), which, by means of reversible complexation, allow for the convenient loading and release of drug molecules. Macrocycles can be attached to IONPs indirectly or directly. Indirect attachment requires the use of small organic linking molecules or conjugation to shell materials. Direct attachment requires neither. We discuss in detail drug release from the macrocycles, highlighting mechanisms that depend on external stimuli such as changes in pH, the competitive binding of ions or small molecules, or the application of ultrasound or electromagnetic radiation.

Sulfonated surface patches of poly(styrene)-based colloidal particles (CPs) were functionalized with cucurbit[7]uril (CB[7]). The macrocycles served as recognition units for diphenyl viologen (DPV(2+)), a rigid bridging ligand. The addition of DPV(2+) to aqueous suspensions of the particles triggered the self-assembly of short linear and branched chainlike structures. The self-assembly mechanism is based on hydrophobic/ion-charge interactions that are established between DPV(2+) and surface-adsorbed CB[7]. DPV(2+) guides the self-assembly of the CPs by forming a ternary DPV(2+)⊂(CB[7])2 complex in which the two CB[7] macrocycles are attached to two different particles. Viologen-driven particle assembly was found to be both directional and reversible. Whereas sodium chloride triggers irreversible particle disassembly, the one-electron reduction of DPV(2+) with sodium dithionite causes disassembly that can be reversed via air oxidation. Thus, this bottom-up synthetic supramolecular approach allowed for the reversible formation and directional alignment of a 2D colloidal material.

Inspired by the discovery of graphene and its unique properties, we focused our research to develop a scheme to create nacre like lamellar structures of molecular sheets of CaCO3 interleaved with an organic material, namely carbon. We developed a facile, chemical template technique, using a formulation of poly(acrylic) acid (PAA) and calcium acetate to create lamellar stacks of single crystal sheets of CaCO3, with a nominal thickness of 17 Å, the same as a unit-cell dimension for calcite (c–axis = 17.062 Å), interleaved with amorphous carbon with a nominal thickness of 8 Å. The strong binding affinity between carboxylate anions and calcium cations in the formulation was used as a molecular template to guide CaCO3 crystallization. Computational modeling of the FTIR spectra showed good agreement with experimental data and confirmed that calcium ions are bridged between polymer chains, resulting in a net-like polymer structure. The process readily lends itself to explore the feasibility of creating molecular sheets of other important inorganic materials and potentially find applications in many fields such as super capacitors and “low k di-electric” systems.

International audience; A series of nanometric isoreticular and/or functionalized analogues of the mesoporous environmentally-friendly iron( III ) polycarboxylates MIL-100/101 have been successfully synthesized. Their exceptional pore size, of up to 68 Å, together with their relatively good stability in solvents, makes them promising candidates for heterogeneous catalysis or inclusion of large molecules, among others.

A fast, efficient and green microwave-assisted synthesis of ultra-small, superparamagnetic iron oxide nanoparticles is reported. By controlling the temperature and heating mode of a polyol reduction using triethylene glycol (TREG) as a green, high-boiling solvent, ultra-small nanoparticles (2-4 nm) exhibiting robust superparamagnetic behavior were obtained. The sizes of the nanoparticles were determined by TEM and DLS measurements. Using a ligand exchange process, the TREG molecules on the surface of the smallest nanoparticles (2 nm) were successfully replaced with Alendronate, an anti-cancer drug molecule, effectively transforming the nanoparticles into a potential theranostic agent.

1 - Article; 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 gamma Fe(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 gamma Fe(2)O(3)@alendronate hybrid nanomaterial reduces cell viability and acts as a drug delivery system. We also investigated the anti-tumoural properties in vivo in nude mice xenografted with MDA-MB-231 tumours. We show that the presence of both gamma Fe(2)O(3)@alendronate and a magnetic field significantly reduced the development of tumours. The amine functionalities can be used as precursor groups for the covalent coupling of peptides or monoclonal antibodies for specific biological targeting. The feasibility of this process was demonstrated by coupling rhodamine B, a fluorescence marker, to the gamma Fe(2)O(3)@alendronate nanohybrid. The system showed fluorescent properties and high affinity for cells. Flow cytometry and fluorescence microscopy were used to study the kinetics of gamma Fe(2)O(3)@alendronate uptake by cells. The magnetic and fluorescent nanoparticles are potential candidates for smart drug-delivery systems. Also, the superparamagnetic behaviour of such nanoparticles may be exploited as MRI contrast agents to improve therapeutic diagnostics.

1 - Article; A new type of multifunctional magnetic nano-platform for bioassays, diagnosis and therapy applications was designed using superparamagnetic gamma Fe(2)O(3) nanoparticles conjugated to hydroxylmethylene bisphosphonate (HMBPs) molecules. The nanoparticle has two essential roles: to act as a probe owing to its specific magnetic properties and to carry on its surface antitumoral molecules (therapeutic applications) or precursor groups for the covalent coupling of biological recognition molecules, such as antibodies, nucleic acids (in vitro & in vivo diagnosis).

1 - Article; We introduce the input of microwave energy to elaborate a multimodal magnetic nanoplatform. This magnetic nanomaterial consists of superparamagnetic gamma Fe(2)O(3) nanoparticles conjugated to hydroxymethylene bisphosphonate (HMBP) molecules with an amine function as the terminal group. The feasibility of such a process is illustrated by the coupling of Rhodamine B to the hybrid magnetic nanomaterial. Using a microwave we manage to have approximately a 50 fold increase in molecules per nanoparticle compared to conventional procedures. Moreover we show that the amount of Rhodamine on the nanoparticle surface could be tuned using various stoichiometric ratios. The presence of Rhodamine B on the nanoparticle surface provides an amphiphilic character to facilitate penetration into the cells.

9 - conference paper: Seventh International Conference on the Scientific and Clinical Applications of Magnetic Carriers; 20-24 May 2008; Vancouver (Canada); Magnetic nanoparticles differing by their size have been synthesized to use them for multiparametric testing, based on their differing magnetic properties. The nanoparticle has two essential roles: to act as a probe owing to its specific magnetic properties and to carry on its surface precursor groups for the covalent coupling of biological recognition molecules, such as antibodies, nucleic acids. A totally unique, newly patented, method has been used to characterize magnetic signatures using the MIAplex technology. The MIAplex reader, developed by Magnisense, measures the non-linear response of the magnetic labels when they are exposed to a multi-frequency alternating magnetic field. This specific signature based on d2B(H)/dH2 was correlated to other more conventional magnetic detection methods (superconducting quantum interference devices (SQUID) and Mössbauer).

1 - Article; Encapsulation into liposomes has been developed in order to allow protection of therapeutical agents against enzymatic degradation, and to reduce doses and toxic side effects. Selective, targeted and controlled release of the drug out of the lipid vesicle is still, however, difficult to achieve. Meanwhile, thanks to their magnetic properties, superparamagnetic iron oxide (SPIO) nanoparticles have also been considered as good delivery vehicles after grafting a therapeutic drug on their surface. A combination of both properties (magnetic targeting and drug encapsulation) is evaluated to deliver an anticancer drug : alendronate, an hydroxymethylene bisphosphonate molecule. gamma-Fe(2)O(3) nanocrystals grafted with alendronate were tested with or without liposome encapsulation, with and without magnetic field, on three human cancer cell lines, MDA-MB231, A431 and U87-MG. Cytotoxicity was measured as well as drug internalization. While results were not identical on the three cell lines with the different formulations, an effective 100% cytotoxic effect could only be achieved with alendronate grafted-SPIO entrapped into liposomes and exposed to a magnetic field.

We report the development of a novel therapeutic nanoplatform, Targeted Chemotherapeutic Nanoparticles (T-CNPs), for the diagnosis and treatment of cancer. The T-CNPs are composed of iron oxide NPs that are functionalized with water-soluble organic nanocontainers - for the encapsulation of a combination of hydrophobic and/or hydrophilic drugs that can act synergistically - and conjugated to cell-penetrating peptides (CPPs) to enhance specific targeting of tumors and internalization into cancer cells. The nanoplatform is designed to simultaneously target a tumor, monitor it by magnetic resonance imaging (MRI), and treat the disease by controlling the gradual release of the delivered anti-cancer drugs using a non-invasive external stimulus, which will concurrently induce hyperthermia. We will highlight new ways for the active release of encapsulated drugs, particularly by an external magnetic field, and promote the understanding of complex in vivo phenomenon when the molecules are optimally delivered. The nanoplatform combines stability, biocompatibility, and dual-purpose functionality (tumor treatment and imaging), with multiple therapeutic strategies (targeted drug delivery and hyperthermia). Our system therefore consolidates diagnosis and targeted therapy into a single, centralized system of treatment. This novel ‘theranostic’ strategy has the potential to pave the way for treatment of cancer in a highly selective and effective, yet relatively sensitive, manner.