Small Hydrodynamic Diameter Research Articles

Targeted chemotherapy for subcutaneous and orthotopic non-small cell lung tumors with cyclic RGD-functionalized and disulfide-crosslinked polymersomal doxorubicin

Lung cancer, with its high mortality and increasing morbidity, has become one of the most lethal malignancies worldwide. Here, we developed cyclic RGD peptide-directed and disulfide-crosslinked polymersomal doxorubicin (cRGD-PS-Dox) as a targeted chemotherapy for human non-small cell lung cancer (NSCLC). Notably, cRGD-PS-Dox exhibited a high Dox loading (15.2 wt.%), small hydrodynamic diameter (96 nm), superb stability, prominent targetability to αvβ3 integrin overexpressing A549 human lung cancer cells, and rapid release of the drug into nuclei, leading to a significantly improved antitumor activity compared with the control groups, i.e., PS-Dox and Lipo-Dox (a liposome injection employed in clinical settings). The pharmacokinetic and biodistribution results for cRGD-PS-Dox revealed similar elimination half-lives but two-fold enhanced tumor accumulation compared with PS-Dox and Lipo-Dox. Intriguingly, cRGD-PS-Dox effectively suppressed the growth of A549 lung tumors in both subcutaneous and orthotopic models with minimal adverse effects at a Dox dose of 12 mg/kg, leading to significant survival benefits compared with PS-Dox and Lipo-Dox. This αvβ3 integrin-targeting multifunctional polymersomal doxorubicin is highly promising for targeted chemotherapy of human NSCLC.

Development of a novel chem-bio hybrid process using biochar supported nanoscale iron sulfide composite and Corynebacterium variabile HRJ4 for enhanced trichloroethylene dechlorination

A sequential chem-bio hybrid process was developed using a novel biochar supported carboxymethyl cellulose-stabilized nanoscale iron sulfide (CMC-FeS@biochar) as a chemical remover and Corynebacterium variabile HRJ4 as a biological agent for trichloroethylene (TCE) degradation. Compared with CMC-FeS, FeS@biochar600, bare FeS and biochar600, the CMC-FeS@biochar600 composite displayed better physiochemical properties (smaller hydrodynamic diameter and higher stability) and demonstrated excellent removal capacity for TCE from aqueous phase. A facultative bacterial strain, Corynebacterium variabile HRJ4, growing well in the presence of CMC-FeS@biochar (added up to 0.25 g L−1), further enhanced TCE removal after chemical treatment. The dechlorination pathway proposed based on the gas chromatography–mass spectrometry (GC-MS) analysis revealed that TCE was dechlorinated to cis-1,2-dichloroethene (cis-DCE) and acetylene via hydrogenolysis and β-elimination, respectively within 12 h by CMC-FeS@biochar. Addition of HRJ4 strain into the reaction system effectively enhanced the degradation of the residual TCE, cis-DCE and acetylene to ethylene. Acetylene was the main product in chemical process, whereas ethylene was the main product in biological process as strain HRJ4 could reduce acetylene to ethylene effectively. The results of this study signify the potential application of CMC-FeS@biochar600/HRJ4 chem-bio hybrid system for complete degradation of TCE in the anaerobic environment.

Effects of Extraction Methods on Physicochemical Properties and Viscosity of Polysaccharides from Orange Peel

In order to take full advantage of the orange peel resource, polysaccharides were extracted from orange peel by hot buffer, chelating agent, dilute alkaline, concentrated alkaline, acid and enzyme extraction, respectively. The physicochemical properties and viscosity of the six polysaccharides were determined. The results showed that the six polysaccharides were mainly consisted of rhamnose, arabinose, galactose and glucose and traces of other monosaccharide. The six polysaccharides exhibited high total carbohydrate (89.74–98.08%), galacturonic acid content (GalA, 8.95–33.16%) and little proteins (<2%). Degree of methoxylation in polysaccharide obtained from orange peel by enzyme extraction and orange peel by acid extraction was higher than the others. They all showed good thermal stability under 84.5°C and non-Newtonian flow behaviors. Polysaccharide obtained from orange peel by hot buffer extraction has higher viscosity than the others at the 0.5% concentration. Polysaccharide obtained from orange peel by dilute alkali extraction appeared the highest viscosity with the increase of concentration, which may be due to the smallest hydrodynamic diameter and the highest rhamnose content.

A Ligand System for the Flexible Functionalization of Quantum Dots via Click Chemistry

AbstractWe present a novel ligand, 5‐norbornene‐2‐nonanoic acid, which can be directly added during established quantum dot (QD) syntheses in organic solvents to generate “clickable” QDs at a few hundred nmol scale. This ligand has a carboxyl group at one terminus to bind to the surface of QDs and a norbornene group at the opposite end that enables straightforward phase transfer of QDs into aqueous solutions via efficient norbornene/tetrazine click chemistry. Our ligand system removes the traditional ligand‐exchange step and can produce water‐soluble QDs with a high quantum yield and a small hydrodynamic diameter of approximately 12 nm at an order of magnitude higher scale than previous methods. We demonstrate the effectiveness of our approach by incubating azido‐functionalized CdSe/CdS QDs with 4T1 cancer cells that are metabolically labeled with a dibenzocyclooctyne‐bearing unnatural sugar. The QDs exhibit high targeting efficiency and minimal nonspecific binding.

A Ligand System for the Flexible Functionalization of Quantum Dots via Click Chemistry.

We present a novel ligand, 5-norbornene-2-nonanoic acid, which can be directly added during established quantum dot (QD) syntheses in organic solvents to generate "clickable" QDs at a few hundred nmol scale. This ligand has a carboxyl group at one terminus to bind to the surface of QDs and a norbornene group at the opposite end that enables straightforward phase transfer of QDs into aqueous solutions via efficient norbornene/tetrazine click chemistry. Our ligand system removes the traditional ligand-exchange step and can produce water-soluble QDs with a high quantum yield and a small hydrodynamic diameter of approximately 12 nm at an order of magnitude higher scale than previous methods. We demonstrate the effectiveness of our approach by incubating azido-functionalized CdSe/CdS QDs with 4T1 cancer cells that are metabolically labeled with a dibenzocyclooctyne-bearing unnatural sugar. The QDs exhibit high targeting efficiency and minimal nonspecific binding.

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats.

Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (−18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.

Improved Fenton Therapy Using Cancer Cell Hydrogen Peroxide

Fenton cancer therapy as a new methodology for the treatment of tumour cells is largely restricted owing to the low stability, high aggregation, and poor selectivity of reported nanoparticles. In this study, an improved approach for the selective destruction of cancer cells is reported. Metal–organic framework (MOF) nanoparticles were synthesized and reduced via a hydrothermal method, and then PEGylated through the surface-initiated atom transfer radical polymerization (SI-ATRP) reaction to produce a PEGylated reduced MOF (P@rMOF). The ratio of PEG to nanoparticles was used to optimize the size and aggregation of the nanoparticles, with 2P@rMOF (2 : 1 mass ratio) having the smallest hydrodynamic diameter. The nanoparticles were further conjugated with folic acid for cell targeting. In vitro cell uptake experiments demonstrated that the internalization of 2P@rMOF-FA nanoparticles into cancer cells (HeLa) was almost 3-fold that of normal cells (NIH-3T3). In the presence of 2P@rMOF-FA, the HeLa cell viability decreased dramatically to 22 %, whereas the NIH-3T3 cell viability remained higher than 80 % after 24 h incubation. The selectivity index for 2P@rMOF-FA is 4.48, which is significantly higher than those reported in the literature for similar strategies. This work thus demonstrates the most stable and selective nanoparticle system for the treatment of cancer cells using the cell’s own H2O2.

Optical glucose sensing using ethanolamine-polyborate complexes.

Wound monitoring is essential to tackle chronic complications at their infancy and thus objectively scrutinize any delay in the epithelization process. Since glucose in wound exudates is recognized as key bio-marker in wound monitoring, the development of a cost-efficient detection method for glucose would aid at tackling early-stage infections in wounds. For the first time, we present a novel platform for one-step synthesis of non-enzymatic, cost-efficient optical glucose sensors. These are based on complexes formed by the interactions between polyborates and ethanolamines. The complexes, synthesized by just heating a solution of boric acid and ethanolamines at 150 °C, were characterized using 13C-NMR, 1H-NMR, 11B-NMR, analytical ultracentrifugation and DFT. The results show that the complexes in solution are extremely small (hydrodynamic diameter of around 0.5 nm) and that the polyborates species interact with the ethanolamines via both moderate and weak hydrogen bondings. These complexes were then tested on glucose concentrations ranging from 0 to 10 mM, showing significant changes in the fluorescent emission between the glucose level expressed in an healable wound (5.0-7.6 mM) and a chronic one (0.3-1.0 mM).

Mesoporous carbon for efficient removal of microcystin-LR in drinking water sources, Nak-Dong River, South Korea: Application to a field-scale drinking water treatment plant

Microcystin-LR (MC-LR) is a growing issue as it is toxic and difficult to remove in drinking water treatment plants (DWTPs). Mesoporous carbon (MC) is evaluated as an alternative adsorbent for MC-LR removal and compared with three widely-used powdered activated carbons (PACs). MC was more favorable for MC-LR removal than PACs. MC-LR adsorption on MC was a rapid process (k2 = 1.02 × 10−4 g/μg/min) that completed within 15 min, while adsorption on PACs took 60 min. The maximum adsorption capacity of MC-LR was 18,008 μg/g (MC), which was higher than that of the PACs. Two mechanisms were associated with adsorption: the small hydro-dynamic diameter of MC in an aqueous solution increased the instantaneous attraction of MC-LR to its surface, and the numerous mesopores enhanced pore diffusion. The MC could remove MC-LR to meet the drinking water guidance level (1 μg/L) from an the MC-LR concentration range of 5–20 μg/L in drinking water sources, and 10 min of treatment was sufficient to meet this level (MC dose = 20 mg/L). The field-scale DWTP was operated by adding 1 or 5 mg/L MC to the mixing basin, and 49.49% and 74.50% of MC-LR was removed, respectively. Geosmin and 2-methylisoborneol were slightly reduced when 5 mg/L of MC was applied.

Augmented glioma-targeted theranostics using multifunctional polymer-coated carbon nanodots.

Overcoming biological barriers to imaging-guided site-specific delivery of therapeutics is the goal of current nanomedicine designs. Here, multifunctional polymer-coated carbon nanodots with an interleukin-6 (IL-6) fragment peptide for receptor-targeting (pCDPI) were prepared for drug delivery. The pCDPI exhibits small hydrodynamic diameters, high water solubility and biocompatibility. Invitro and invivo results demonstrated that pCDPI can overcome the blood-brain barrier (BBB) and deeply penetrate into orthotopic glioma in mice, to inhibit IL-6-induced cell proliferation and achieve imaging-guided targeted drug delivery. Simultaneously, a pH-sensitive sustained release of doxorubicin (DOX) accompanied with real-time fluorescence monitoring was realized. A distinct synergistic therapeutic outcome could be achieved which suggests the presented nanomedicine having promising potential for future cancer treatments.

Chronic ZnO-NPs exposure at environmentally relevant concentrations results in metabolic and locomotive toxicities in Caenorhabditis elegans

ZnO nanoparticles (ZnO-NPs) are emerging contaminants that raise the concerns of potential risk in the aquatic environment. It has been estimated that the environmental ZnO-NPs concentration is 76 μg/l in the aquatic environment. Our aim was to determine the aquatic toxicity of ZnO-NPs with chronic exposure at environmentally relevant concentrations using the nematode Caenorhabditis elegans. Two simulated environmentally relevant mediums—moderately hard reconstituted water (EPA water) and simulated soil pore water (SSPW)—were used to represent surface water and pore water in sediment, respectively. The results showed that the ZnO-NPs in EPA water has a much smaller hydrodynamic diameter than that in SSPW. Although the ionic release of Zn ions increased time-dependently in both mediums, the Zn ions concentrations in EPA water increased two-fold more than that in SSPW at 48 h and 72 h. The ZnO-NPs did not induce growth defects or decrease head thrashes in C. elegans in either media. However, chronic exposure to ZnO-NPs caused a significant reduction in C. elegans body bends in EPA water even with a relatively low concentration (0.05 μg/l); similar results were not observed in SSPW. Moreover, at the same concentrations (50 and 500 μg/l), body bends in C. elegans were reduced more severely in ZnO-NPs than in ZnCl2 in EPA water. The ATP levels were consistently and significantly decreased, and ROS was induced after ZnO-NPs exposure (50 and 500 μg/l) in EPA water. Our results provide evidences that chronic exposure to ZnO-NPs under environmentally relevant concentrations causes metabolic and locomotive toxicities implicating the potential ecotoxicity of ZnO-NPs at low concentrations in aquatic environments.

Dispersion of atmospheric fine particulate matters in simulated lung fluid and their effects on model cell membranes

Atmospheric fine particulate matter (PM2.5) was collected to investigate its dispersion in simulated lung fluid (SLF) and its interaction with model cell membranes. Organic acids, NH4+, SO42− and NO3− were detected in PM2.5 soluble fraction, and heavy metals were detected from the total mass. The insoluble fraction contained kaolinite, CaCO3, aliphatic carbons, aromatic rings, carboxyl and hydroxyl groups reflected by the infrared spectra. Proteins dispersed PM2.5 in SLF, resulted in smaller hydrodynamic diameter (dH) and slower sedimentation rate. Conversely, phospholipids increased dH value and accelerated sedimentation rate. Giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) were used as model cell membranes. PM2.5 adhered on and disrupted the membrane containing positively-charged lipids but not the membrane containing neutrally- and negatively-charged lipids, which was monitored by microscopy and a quartz crystal microbalance with dissipation (QCM-D). The cationic sites on membrane were necessary for PM2.5 adhesion, but membrane should be disrupted by the combined action of electrostatic forces and hydrogen bonds between PM2.5 oxygen containing groups and the lipid phosphate groups. Our results specified the roles of proteins and phospholipids in PM2.5 dispersion and transport, highly suggested that the health hazard of PM2.5 was related to the biomolecules in the lung fluid and the particle surface groups.

Photodegradation of Mercaptopropionic Acid- and Thioglycollic Acid-Capped CdTe Quantum Dots in Buffer Solutions.

CdTe quantum dots (QDs) were synthesized by 3-mercaptopropionic acid (MPA) and thioglycollic acid (TGA) as capping agents. It is confirmed that TGA and MPA molecules were attached on the surface of the QDs using Fourier transform infrared (FT-IR) spectra. The movement of the QDs in agarose gel electrophoresis indicated that MPA-capped CdTe QDs had small hydrodynamic diameter. The photoluminescence (PL) intensity of TGA-capped QDs is higher than that of MPA-capped QDs at same QD concentration because of the surface passivation of TGA. To systemically investigate the photodegradation, CdTe QDs with various PL peak wavelengths were dispersed in phosphate buffered saline (PBS) and Tris-borate-ethylenediaminetetraacetic acid (TBE) buffer solutions. It was found that the PL intensity of the QDs in PBS decreased with time. The PL peak wavelengths of the QDs in PBS solutions remained unchanged. As for TGA-capped CdTe QDs, the results of PL peak wavelengths in TBE buffer solutions indicated that S(2-) released by TGA attached to Cd(2+) and formed CdS-like clusters layer on the surface of aqueous CdTe QDs. In addition, the number of TGA on the CdTe QDs surface was more than that of MPA. When the QDs were added to buffer solutions, agents were removed from the surface of CdTe QDs, which decreased the passivation of agents thus resulted in photodegradation of CdTe QDs in buffer solutions.

Linker histone partial phosphorylation: effects on secondary structure and chromatin condensation.

Linker histones are involved in chromatin higher-order structure and gene regulation. We have successfully achieved partial phosphorylation of linker histones in chicken erythrocyte soluble chromatin with CDK2, as indicated by HPCE, MALDI-TOF and Tandem MS. We have studied the effects of linker histone partial phosphorylation on secondary structure and chromatin condensation. Infrared spectroscopy analysis showed a gradual increase of β-structure in the phosphorylated samples, concomitant to a decrease in α-helix/turns, with increasing linker histone phosphorylation. This conformational change could act as the first step in the phosphorylation-induced effects on chromatin condensation. A decrease of the sedimentation rate through sucrose gradients of the phosphorylated samples was observed, indicating a global relaxation of the 30-nm fiber following linker histone phosphorylation. Analysis of specific genes, combining nuclease digestion and qPCR, showed that phosphorylated samples were more accessible than unphosphorylated samples, suggesting local chromatin relaxation. Chromatin aggregation was induced by MgCl2 and analyzed by dynamic light scattering (DLS). Phosphorylated chromatin had lower percentages in volume of aggregated molecules and the aggregates had smaller hydrodynamic diameter than unphosphorylated chromatin, indicating that linker histone phosphorylation impaired chromatin aggregation. These findings provide new insights into the effects of linker histone phosphorylation in chromatin condensation.

Gold Nanoclusters‐Based Nanoprobes for Simultaneous Fluorescence Imaging and Targeted Photodynamic Therapy with Superior Penetration and Retention Behavior in Tumors

Gold nanoclusters (GNCs) attract increasing attention due to their potential applications in sensing, catalysis, optoelectronics, and biomedicine. Herein, the formation of highly fluorescent glutathione (GSH)‐capped GNCs is achieved through the delicate control of the reduction kinetics and thermodynamic selection of the Au(I)–SG complexes. Furthermore, the GNCs‐based nanoprobes are developed by the covalent coupling folic acid (FA) and PEG (polyethylene glycol) on the surface of GNCs directly, followed by trapping photosensitizer (chlorin e6, Ce6) within PEG networks and attaching to the GNCs surface. The fabricated nanoprobes (Ce6@GNCs‐PEG2K‐FA) possess a uniform particle size (hydrodynamic diameter ≈6.1 ± 1.2 nm), without affecting the yield of singlet oxygen of the trapped Ce6. In vitro studies show the enhanced cellular uptake and satisfactory photodynamic therapy (PDT) effectiveness toward MGC‐803 cells when compared with free Ce6. The biodistribution and excretion pathway studies of the nanoprobes in MGC‐803 tumor‐bearing nude mice reveal their superior penetration and retention behavior in tumors, while the preserved features of renal clearance and stealthy to reticulo‐endothelial system are mainly attributed to the small hydrodynamic diameters and the FA‐capped PEGylated ligands. The enhanced PDT efficacy and the nontoxicity to mice provide an exciting new nano‐platform with promising clinical translational potential.

One-pot one-cluster synthesis of fluorescent and bio-compatible Ag14 nanoclusters for cancer cell imaging.

Small-molecule-protected silver nanoclusters have smaller hydrodynamic diameter, and thus may hold greater potential in biomedicine application compared with the same core-sized, macromolecule (i.e. DNA)-protected silver nanoclusters. However, the live cell imaging labeled by small-molecule-protected silver nanoclusters has not been reported until now, and the synthesis and atom-precise characterization of silver nanoclusters have been challenging for a long time. We develop a one-pot one-cluster synthesis method to prepare silver nanoclusters capped with GSH which is bio-compatible. The as-prepared silver nanoclusters are identified to be Ag14(SG)11 (abbreviated as Ag14, SG: glutathione) by isotope-resolvable ESI-MS. The structure is probed by 1D NMR spectroscopy together with 2D COSY and HSQC. This cluster species is fluorescent and the fluorescence quantum yield is solvent-dependent. Very importantly, Ag14 was successfully applied to label lung cancer cells (A549) for imaging, and this work represents the first attempt to image live cells with small-molecule-protected silver nanoclusters. Furthermore, it is revealed that the Ag14 nanoclusters exhibit lower cytotoxicity compared with some other silver species (including silver salt, silver complex and large silver nanoparticles), and the explanation is also provided. The comparison of silver nanoclusters to state-of-the-art labeling materials in terms of cytotoxicity and photobleaching lifetime is also conducted.

Gold nanoparticles obtained by aqueous digestive ripening: Their application as X-ray contrast agents

A preparative protocol to synthesize large quantities of size-controlled gold nanoparticles (Au NPs), stabilized by CH3O-PEG5000-SH (PEG-SH) in aqueous medium, is reported. The combination of metal vapor synthesis (MVS) technique with digestive ripening process allowed to obtain PEGylated Au NPs with mean core particle size of 3.8nm and hydrodynamic diameters centered at 8.0nm which were effectively used as computed tomography (CT) contrast agents for in vivo experiments on mice. The surface functionalization together with the small hydrodynamic diameters of the engineered Au nanoparticles permitted their efficient renal clearance, still retaining a prolonged blood circulation and a stealth capability.

Collagen-based silver nanoparticles for biological applications: synthesis and characterization.

BackgroundType I collagen is an abundant natural polymer with several applications in medicine as matrix to regenerate tissues. Silver nanoparticles is an important nanotechnology material with many utilities in some areas such as medicine, biology and chemistry. The present study focused on the synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility. Three formulations of AgNPcol were physicochemical characterized, antibacterial activity in vitro and cell viability assays were analyzed. AgNPcol was characterized by means of the following: ultraviolet–visible spectroscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy, atomic absorption analysis, transmission electron microscopy and of X-ray diffraction analysis.ResultsAll AgNPcol showed spherical and positive zeta potential. The AgNPcol at a molar ratio of 1:6 showed better characteristics, smaller hydrodynamic diameter (64.34 ± 16.05) and polydispersity index (0.40 ± 0.05), and higher absorbance and silver reduction efficiency (0.645 mM), when compared with the particles prepared in other mixing ratios. Furthermore, these particles showed antimicrobial activity against both Staphylococcus aureus and Escherichia coli and no toxicity to the cells at the examined concentrations.ConclusionsThe resulted particles exhibited favorable characteristics, including the spherical shape, diameter between 64.34 nm and 81.76 nm, positive zeta potential, antibacterial activity, and non-toxicity to the tested cells (OSCC).Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-014-0036-6) contains supplementary material, which is available to authorized users.

Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment.

AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (<5 nm) and they are biodegradable through hydrolysis of siloxane bonds. Such degradation was evaluated in diluted conditions at physiological pH by dynamic light scattering and relaxometry. AGuIX nanoparticles are also known as positive contrast agents and efficient radiosensitizers. The aim of this paper is to compare their efficiency for magnetic resonance imaging and radiosensitization to those of the commercial gadolinium based molecular agent: DOTAREM®. An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal. The better contrast obtained after injection of Aguix than DOTAREM® is due to a higher longitudinal relaxivity and a residential time in the blood circulation that is two times higher. A fast and large increase in the contrast is also observed by MRI after an intravenous injection of the AGuIX in 9 L gliosarcoma bearing rats, and a plateau is reached seven minutes after the injection.We established a radiotherapy protocol consisting of an irradiation by microbeam radiation therapy 20 minutes after the injection of a specific quantity of gadolinium. After microbeam radiation therapy, no notable difference in median survival time was observed in the presence or absence of gadolinium chelates (38 and 44 days respectively). In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol. This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.

Caseinomacropeptide modifies the heat-induced denaturation–aggregation process of β-lactoglobulin

The effect of caseinomacropeptide (CMP) concentration on the kinetics of denaturation of β-lactoglobulin (β-Lg) and on the size and structure of the heat-induced aggregates was investigated over a wide range of pH (3.0–6.7) and temperature (65–95 °C). Irrespective of pH and heating temperature, CMP increased the rate of β-Lg denaturation. When β-Lg and CMP were negatively charged (i.e., at pH 6.7), increasing CMP concentration hindered aggregate formation; the aggregates had a smaller hydrodynamic diameter and the protein solution turbidity decreased. However, when β-Lg and CMP were oppositely charged (i.e., at pH 4.0), CMP promoted aggregate formation and large particles (>5 μm) were formed on heating. Nevertheless, the covalent aggregates constituting these large particles were of smaller size than those formed on heating β-Lg in the absence of CMP. At pH 4.0, CMP induced the formation of large particles when added in a solution of preformed aggregates of β-Lg.