Impact of Lipid Composition on Vesicle Protein Adsorption: A BSA Case Study.

Investigating the interaction between liposomes and proteins is of paramount importance in the development of liposomal formulations with real potential for bench-to-bedside transfer. Upon entering the body, proteins are immediately adsorbed on the liposomal surface, changing the nanovehicles' biological identity, which has a significant impact on their biodistribution and pharmacokinetics and ultimately on their therapeutic effect. Albumin is the most abundant plasma protein and thus usually adsorbs immediately on the liposomal surface. We herein report a comprehensive investigation on the adsorption of model protein bovine serum albumin (BSA) onto liposomal vesicles containing the zwitterionic lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), in combination with either cholesterol (CHOL) or the cationic lipid 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP). While many studies regarding protein adsorption on the surface of liposomes with different compositions have been performed, to the best of our knowledge, the differential responses of CHOL and DOTAP upon albumin adsorption on vesicles have not yet been investigated. UV-vis spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a strong influence of the phospholipid membrane composition on protein adsorption. Hence, it was found that DOTAP-containing vesicles adsorb proteins more robustly but also aggregate in the presence of BSA, as confirmed by DLS and TEM. Separation of liposome-protein complexes from unadsorbed proteins performed by means of centrifugation and size exclusion chromatography (SEC) was also investigated. Our results show that neither method can be regarded as a golden experimental setup to study the protein corona of liposomes. Yet, SEC proved to be more successful in the separation of unbound proteins, although the amount of lipid loss upon liposome elution was higher than expected. In addition, coarse-grained molecular dynamics simulations were employed to ascertain key membrane parameters, such as the membrane thickness and area per lipid. Overall, this study highlights the importance of surface charge and membrane fluidity in influencing the extent of protein adsorption. We hope that our investigation will be a valuable contribution to better understanding protein-vesicle interactions for improved nanocarrier design.

Current trends in luminescence-based assessment of apoptosis.

Apoptosis, the most extensively studied type of cell death, is known to play a crucial role in numerous processes such as elimination of unwanted cells or cellular debris, growth, control of the immune system, and prevention of malignancies. Defective regulation of apoptosis can trigger various diseases and disorders including cancer, neurological conditions, autoimmune diseases and developmental disorders. Knowing the nuances of the cell death type induced by a compound can help decipher which therapy is more effective for specific diseases. The detection of apoptotic cells using classic methods has brought significant contribution over the years, but innovative methods are quickly emerging and allow more in-depth understanding of the mechanisms, aside from a simple quantification. Due to increased sensitivity, time efficiency, pathway specificity and negligible cytotoxicity, these innovative approaches have great potential for both in vitro and in vivo studies. This review aims to shed light on the importance of developing and using novel nanoscale methods as an alternative to the classic apoptosis detection techniques.

Co-delivery of gemcitabine and salinomycin in PEGylated liposomes for enhanced anticancer efficacy against colorectal cancer.

Colorectal cancer remains one of the major causes of morbidity and mortality in both developed and emerging countries. Cancer stem cells (CSCs) are a subpopulation of cells within the tumor mass harboring stem cell characteristics, considered responsible for tumor initiation, growth, relapse, and treatment failure. Lately, it has become clear that both CSCs and non-CSCs have to be eliminated for the successful eradication of cancer. Drug delivery systems have been extensively employed to enhance drug efficacy. In this study, salinomycin (SAL), a selective anti-CSC drug, and gemcitabine (GEM), a conventional anticancer drug, were co-loaded in liposomes and tested for optimal therapeutic efficacy. We employed the Design of Experiments approach to develop and optimize a liposomal delivery system for GEM and SAL. The antiproliferative effect of the liposomes was evaluated in SW-620 human colorectal cancer cells. The GEM and SAL-loaded liposomes exhibited adequate size, polydispersity, zeta potential, and drug content. The in vitro release study showed a sustained release of GEM and SAL from the liposomes over 72 h. Moreover, no sign of liposome aggregation was seen over 1 month and in a biological medium (FBS). The in vitro cytotoxic effects of the co-loaded liposomes were superior to that of single GEM either in free or liposomal form. The combination therapy using GEM and SAL co-loaded in liposomes could be a promising strategy for tackling colorectal cancer.

Hybrid Lipid Nanoformulations for Hepatoma Therapy: Sorafenib Loaded Nanoliposomes-A Preliminary Study.

Sorafenib is a multikinase inhibitor that has received increasing attention due to its high efficacy in hepatocellular carcinoma treatment. However, its poor pharmacokinetic properties (limited water solubility, rapid elimination, and metabolism) still represent major bottlenecks that need to be overcome in order to improve Sorafenib's clinical application. In this paper, we propose a nanotechnology-based hybrid formulation that has the potential to overcome these challenges: sorafenib-loaded nanoliposomes. Sorafenib molecules have been incorporated into the hydrophobic lipidic bilayer during the synthesis process of nanoliposomes using an original procedure developed in our laboratory and, to the best of our knowledge, this is the first paper reporting this type of analysis. The liposomal hybrid formulations have been characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA) that provided useful information concerning their shape, size, zeta-potential, and concentration. The therapeutic efficacy of the nanohybrids has been evaluated on a normal cell line (LX2) and two hepatocarcinoma cell lines, SK-HEP-1 and HepG2, respectively.

The Effect of Zn-Substitution on the Morphological, Magnetic, Cytotoxic, and In Vitro Hyperthermia Properties of Polyhedral Ferrite Magnetic Nanoparticles.

The clinical translation of magnetic hyperthermia (MH) needs magnetic nanoparticles (MNPs) with enhanced heating properties and good biocompatibility. Many studies were devoted lately to the increase in the heating power of iron oxide MNPs by doping the magnetite structure with divalent cations. A series of MNPs with variable Zn/Fe molar ratios (between 1/10 and 1/1) were synthesized by using a high-temperature polyol method, and their physical properties were studied with different techniques (Transmission Electron Microscopy, X-ray diffraction, Fourier Transform Infrared Spectroscopy). At low Zn doping (Zn/Fe ratio 1/10), a significant increase in the saturation magnetization (90 e.m.u./g as compared to 83 e.m.u./g for their undoped counterparts) was obtained. The MNPs' hyperthermia properties were assessed in alternating magnetic fields up to 65 kA/m at a frequency of 355 kHz, revealing specific absorption rates of up to 820 W/g. The Zn ferrite MNPs showed good biocompatibility against two cell lines (A549 cancer cell line and BJ normal cell line) with a drop of only 40% in the viability at the highest dose used (500 µg/cm2). Cellular uptake experiments revealed that the MNPs enter the cells in a dose-dependent manner with an almost 50% higher capacity of cancer cells to accommodate the MNPs. In vitro hyperthermia data performed on both cell lines indicate that the cancer cells are more sensitive to MH treatment with a 90% drop in viability after 30 min of MH treatment at 30 kA/m for a dose of 250 µg/cm2. Overall, our data indicate that Zn doping of iron oxide MNPs could be a reliable method to increase their hyperthermia efficiency in cancer cells.

Quantifying Cytosolic Cytochrome c Concentration Using Carbon Quantum Dots as a Powerful Method for Apoptosis Detection.

BACKGROUND: Cytochrome c (Cyt c) is a key biomarker for early apoptosis, and many methods were designed to detect its release from mitochondria. For a proper evaluation of these programed cell death mechanisms, fluorescent nanoparticles are excellent candidates due to their valuable optical properties. Among all classes of nanoparticles developed thus far, carbon-based quantum dots bring qualitative and efficient imaging strategies for biomedical applications as a consequence of their biocompatibility and low cytotoxicity. METHODS: In this study, we synthesized carbon quantum dots smaller than 5 nm from sodium citrate and polyethylene imine. These nanoparticles were rigorously characterized, and their quenching capacity in apoptotic events was assessed in A549 cells treated with staurosporine and etoposide. For the evaluation of Cyt c release, a phenomenon directly correlated with apoptotic events, we ran a semiquantitative analysis using confocal laser scanning microscopy. RESULTS: Carbon quantum dots were synthesized and were successfully employed for Cyt c detection by means of fluorescence microscopy. Significant drops in fluorescence intensity were observed in the case of cells treated with apoptosis-inducing therapeutic compounds compared to untreated cells, confirming Cyt c release from mitochondria to cytosol. CONCLUSION: Considering these results, we strongly believe this method can contribute to an indirect in vitro evaluation of apoptosis.

Testing the Limits of a Portable NIR Spectrometer: Content Uniformity of Complex Powder Mixtures Followed by Calibration Transfer for In-Line Blend Monitoring.

(1) Background: Portable NIR spectrometers gain more and more ground in the field of Process Analytical Technology due to the easy on-site flexibility and interfacing versatility. These advantages that originate from the instrument miniaturization, also come with a downside with respect to performance compared to benchtop devices. The objective of this work was to evaluate the performance of MicroNIR in a pharmaceutical powder blend application, having three active ingredients and 5 excipients. (2) Methods: Spectral data was recorded in reflectance mode using static and dynamic acquisition, on calibration set samples developed using an experimental design. (3) Results: The developed method accurately predicted the content uniformity of these complex mixtures, moreover it was validated in the entire calibration range using ±10% acceptance limits. With respect to at-line prediction, the method presented lower performance compared to a previously studied benchtop spectrometer. Regarding the in-line monitoring of the blending process, it was shown that the spectral variability-induced by dynamic acquisition could be efficiently managed using spectral pre-processing. (4) Conclusions: The in-line process monitoring resulted in accurate concentration profiles, highlighting differences in the mixing behaviour of the investigated ingredients. For the low dose component homogeneity was not reached due to an inefficient dispersive mixing.

Percutaneous ultrasound guided PEG-coated gold nanoparticles enhanced radiofrequency ablation in liver.

To investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones' volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm3, 19.22 ± 5.77 cm3, and 8.80 ± 3.33 cm3 for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.

Transforming growth factor ß-mediated micromechanics modulates disease progression in primary myelofibrosis.

Primary myelofibrosis (PMF) is a Ph-negative myeloproliferative neoplasm (MPN), characterized by advanced bone marrow fibrosis and extramedullary haematopoiesis. The bone marrow fibrosis results from excessive proliferation of fibroblasts that are influenced by several cytokines in the microenvironment, of which transforming growth factor-ß (TGF-ß) is the most important. Micromechanics related to the niche has not yet been elucidated. In this study, we hypothesized that mechanical stress modulates TGF-ß signalling leading to further activation and subsequent proliferation and invasion of bone marrow fibroblasts, thus showing the important role of micromechanics in the development and progression of PMF, both in the bone marrow and in extramedullary sites. Using three PMF-derived fibroblast cell lines and transforming growth factor-ß receptor (TGFBR) 1 and 2 knock-down PMF-derived fibroblasts, we showed that mechanical stress does stimulate the collagen synthesis by the fibroblasts in patients with myelofibrosis, through the TGFBR1, which however seems to be activated through alternative pathways, other than TGFBR2.

In Vitro Intracellular Hyperthermia of Iron Oxide Magnetic Nanoparticles, Synthesized at High Temperature by a Polyol Process.

We report the synthesis of magnetite nanoparticles (IOMNPs) using the polyol method performed at elevated temperature (300 °C) and high pressure. The ferromagnetic polyhedral IOMNPs exhibited high saturation magnetizations at room temperature (83 emu/g) and a maximum specific absorption rate (SAR) of 2400 W/gFe in water. The uniform dispersion of IOMNPs in solid matrix led to a monotonous increase of SAR maximum (3600 W/gFe) as the concentration decreased. Cytotoxicity studies on two cell lines (cancer and normal) using Alamar Blues and Neutral Red assays revealed insignificant toxicity of the IOMNPs on the cells up to a concentration of 1000 µg/mL. The cells internalized the IOMNPs inside lysosomes in a dose-dependent manner, with higher amounts of IOMNPs in cancer cells. Intracellular hyperthermia experiments revealed a significant increase in the macroscopic temperatures of the IOMNPs loaded cell suspensions, which depend on the amount of internalized IOMNPs and the alternating magnetic field amplitude. The cancer cells were found to be more sensitive to the intracellular hyperthermia compared to the normal ones. For both cell lines, cells heated at the same macroscopic temperature presented lower viability at higher amplitudes of the alternating magnetic field, indicating the occurrence of mechanical or nanoscale heating effects.

Clinical indications and radiation doses of cone beam computed tomography in orthodontics.

Cone beam computed tomography can be used in pediatric population when a tridimensional analysis of dental and maxillofacial bone structures is required. Even though CBCT is considered a low dose radiological examination, ionizing radiation is a known human carcinogenic factor. Furthermore, biological effects are more important in young patients because of their higher radiosensitivity. Orthodontic treatment is typically initiated at young ages and the most common radiographs at this age are dental. This makes it important to quantify the effects of diagnostic radiographs, in particular of CBCT, due to the fact that the radiation doses are higher compared to conventional radiological methods. So far, the carcinogenic response after low dose radiation exposure is not fully understood in the scientific literature. The aim of our review was to emphasize the main indications of CBCT in orthodontics and to evaluate the radiation doses and potential risks of CBCT irradiation of pediatric patients.

Hyperthermia, Cytotoxicity, and Cellular Uptake Properties of Manganese and Zinc Ferrite Magnetic Nanoparticles Synthesized by a Polyol-Mediated Process.

Manganese and zinc ferrite magnetic nanoparticles (MNPs) were successfully synthesizedusing the polyol method in ethylene glycol and were found to have high saturation magnetizationvalues (90-95 emu/g at 4 K) when formed by ~30-nm crystallites assembled in an ~80-nm multicorestructure. Hyperthermia data revealed a sigmoidal dependence of the specific absorption rate (SAR)on the alternating magnetic field (AMF) amplitude, with remarkable saturation SAR values in waterof ~1200 W/gFe+Mn and ~800 W/gFe+Zn for the Mn and Zn ferrites, respectively. The immobilizationof the MNPs in a solid matrix reduced the maximum SAR values by ~300 W/gFe+Mn, Zn for bothferrites. The alignment of the MNPs in a uniform static magnetic field, before their immobilizationin a solid matrix, significantly increased their heating performance. Toxicity assays performed infour cell lines revealed a lower toxicity for the Mn ferrites, while in the case of the Zn ferrites, only~50% of cells were viable upon their incubation for 24 h with 0.2 mg/mL of MNPs. Cellular uptakeexperiments revealed that both MNPs entered the cells in a time-dependent manner, as they werefound initially in endosomes and later in the cytosol. All of the studied cell lines were more sensitiveto the ZnFe2O4 MNPs.

SERS-based differential diagnosis between multiple solid malignancies: breast, colorectal, lung, ovarian and oral cancer.

PURPOSE: Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer. PATIENTS AND METHODS: Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532 nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis-linear discriminant analysis (PCA-LDA). RESULTS: The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer. CONCLUSION: SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.

Gold nanorods: from anisotropy to opportunity. An evolution update.

Gold nanoparticles have drawn attention to nanomedicine for many years due to their physicochemical properties, which include: good stability; biocompatibility; easy surface chemistry and superior magnetic; and last, electronic properties. All of these properties distinguish gold nanoparticles as advantageous carriers to be exploited. The challenge to develop new gold nanostructures has led to anisotropy, a new property to exploit for various medical applications: diagnostic and imaging strategies as well as therapeutic options. Gold nanorods are the most studied anisotropic gold nanoparticles because of the presence of two absorption peaks according to their longitudinal and transversal plasmon resonances. The longitudinal surface plasmonic resonance can provide the absorption in the near-infrared region and this is an important aspect of using gold nanorods for medical purposes.

Exosome-carried microRNA-based signature as a cellular trigger for the evolution of chronic lymphocytic leukemia into Richter syndrome.

Even if considered a cumulative and not a proliferative CD5+ B-cell neoplasm, chronic lymphocytic leukemia (CLL) has a proliferation rate higher than that recognized earlier, especially in the lymphoid tissues. Some patients with CLL develop a clinical syndrome entitled Richter syndrome (RS). Understanding CLL genetics and epigenetics may help to elucidate the molecular basics of the clinical heterogeneity of this type of malignancy. In the present project we aimed to identify a microRNA species that can predict the evolution of therapy-resistant CLL towards RS. In the first phase of our study, microRNA-19b was identified as a possible target, and in the second phase, we transfected three different CLL cell lines with microRNA-19b mimic and inhibitor and assessed the potential role on leukemia cells in vitro. The mechanism by which miR-19b acts were identified as the upregulation of Ki67 and downregulation of p53. This was further supported through RT-PCR and western blotting on CLL cell lines, as well as by next generation sequencing on two patients diagnosed with CLL that evolved into RS.

Origanum vulgare mediated green synthesis of biocompatible gold nanoparticles simultaneously possessing plasmonic, antioxidant and antimicrobial properties.

PURPOSE: The leaves and flowering stem of Origanum vulgare contain essential oils, flavonoids, phenolic acids and anthocyanins. We propose a new, simple, one-pot, O. vulgare extract (OVE) mediated green synthesis method of biocompatible gold nanoparticles (AuNPs) possessing improved antioxidant, antimicrobial and plasmonic properties. MATERIALS AND METHODS: Different concentrations of OVEs were used to reduce gold ions and to synthetize biocompatible spherical AuNPs. Their morphology and physical properties have been investigated by means of transmission electron microscopy, ultraviolet-visible absorption spectroscopy, photon correlation spectroscopy and Fourier transform infrared spectroscopy, whereas their plasmonic properties have been tested using surface-enhanced Raman spectroscopy (SERS). The antioxidant properties of nanoparticles (NPs) have been evaluated by 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and the antimicrobial tests were performed using the disk diffusion assay. Their cytotoxicity has been assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: The experimental results confirmed the successful synthesis of biocompatible, spherical, plasmonic NPs having a mean diameter of ~40 nm and an outstanding aqueous stability. This new class of NPs exhibits a very good antioxidant activity and presents interesting inhibitory effects against Staphylococcus aureus and Candida albicans. Due to their plasmonic properties, AuNPs are used as SERS substrates for the detection of a test molecule (methylene blue) up to a concentration of 10-7 M and a pharmaceutical compound (propranolol) in solution. Cytotoxicity assays revealed that AuNPs are better tolerated by normal human dermal fibroblast cells, while the melanoma cancer cells are more sensitive. CONCLUSION: The biocompatible AuNPs synthetized using OVEs showed significant bactericidal and antimycotic activities, the most sensitive microorganisms being S. aureus and C. albicans, both commonly involved in various dermatological infections. Moreover, the significant antioxidant effect might recommend their use for protective and/or preventive effect in various skin inflammatory conditions, including the reduction in side effects in dermatological infections. Meanwhile, the as-synthesized biocompatible AuNPs can be successfully used as SERS substrates for the detection of pharmaceutical compounds in aqueous solutions.

The silent healer: miR-205-5p up-regulation inhibits epithelial to mesenchymal transition in colon cancer cells by indirectly up-regulating E-cadherin expression.

EMT represents the dominant program within advanced stages of colon cancer, where cells acquire migratory characteristics in order to invade secondary tissues and form metastasis. Where the majority of the therapeutic strategies are concentrated on the reduction of the tumor mass through different apoptotic mechanisms, the present study advocates an important role for miR-205-5p in impairment of colon cancer cells migration and restoration of the epithelial phenotype. Upon identification of a homogenous downregulated profile for miR-205-5p in colon adenocarcinoma patients, functional studies demonstrated that experimental upregulation of this sequence is able to significantly raise the levels of E-cadherin through direct inhibition of ZEB1. Moreover, the elevation in CDH1 expression was translated into functional parameters where cells lost their invasion and migratory characteristics and formed homogenous clusters through adhesion interactions. Survival analysis of colon adenocarcinoma patients revealed that low levels of miR-205-5p are associated with an unfavorable prognostic compared to those with increased expression, demonstrating the possible clinical utility of miR-205-5p replacement. Exogenous administration of miRNA mimics was not associated with significant changes in cell viability or inflammatory pathways. Therefore, the proposed strategy is aiming towards inhibition of metastasis and limitation of the tumor borders in advanced stages patients in order to prolong the survival time and to increase the efficiency of the current therapeutic strategies.

Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties.

Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe3O4-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of ~1400 W/gMNP for the small monocrystalline MNPs and only 400 W/gMNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism.

Polyethylene Glycol-Mediated Synthesis of Cubic Iron Oxide Nanoparticles with High Heating Power.

Iron oxide magnetic nanoparticles (IOMNPs) have been successfully synthesized by means of solvothermal reduction method employing polyethylene glycol (PEG200) as a solvent. The as-synthesized IOMNPs are poly-dispersed, highly crystalline, and exhibit a cubic shape. The size of IOMNPs is strongly dependent on the reaction time and the ration between the amount of magnetic precursor and PEG200 used in the synthesis method. At low magnetic precursor/PEG200 ratio, the cubic IOMNPs coexist with polyhedral IOMNPs. The structure and morphology of the IOMNPs were thoroughly investigated by using a wide range of techniques: TEM, XRD, XPS, FTIR, and RAMAN. XPS analysis showed that the IOMNPs comprise a crystalline magnetite core bearing on the outer surface functional groups from PEG200 and acetate. The presence of physisorbed PEG200 on the IOMNP surface is faintly detected through FT-IR spectroscopy. The surface of IOMNPs undergoes oxidation into maghemite as proven by RAMAN spectroscopy and the occurrence of satellite peaks in the Fe2p XP spectra. The magnetic studies performed on powder show that the blocking temperature (TB) of IOMNPs is around 300 K displaying a coercive field in between 160 and 170 Oe. Below the TB, the field-cooled (FC) curves turn concave and describe a plateau indicating that strong magnetic dipole-dipole interactions are manifested in between IOMNPs. The specific absorption rate (SAR) values increase with decreasing nanoparticle concentrations for the IOMNPs dispersed in water. The SAR dependence on the applied magnetic field, studied up to magnetic field amplitude of 60 kA/m, presents a sigmoid shape with saturation values up to 1700 W/g. By dispersing the IOMNPs in PEG600 (liquid) and PEG1000 (solid), it was found that the SAR values decrease by 50 or 75 %, indicating that the Brownian friction within the solvent was the main contributor to the heating power of IOMNPs.

A new class of pegylated plasmonic liposomes: synthesis and characterization.

The multifunctional nanoobjects that can be controlled, manipulated and triggered using external stimuli represent very promising candidates for nanoscale therapeutic and diagnostic applications. In this study we report the successful synthesis and characterization of a new class of very stable multifunctional nanoobjects, containing cationic liposomes decorated with PEGylated gold nanoparticles (PEGAuNPs). The multifunctional hybrid nanoobjects (mHyNp) were prepared by taking advantage of the electrostatic interactions between small unilamelar cationic liposomes and negatively charged gold nanoparticles. The mHyNps have been investigated by UV-VIS absorption spectroscopy, Dynamic Light Scattering (DLS), Zeta Potential Measurements and Transmission Electron Microscopy (TEM). The TEM images clearly revealed the attachment of individual gold nanoparticles onto the spherical outer surface of the cationic liposomes which was also confirmed by DLS and UV-VIS data. Furthermore, the plasmonic properties of the hybrid complexes have been evaluated by using the Surface Enhanced Raman Spectroscopy (SERS) technique. It is shown that PEG mediated interaction between the liposomes and the gold nanoparticles enabled the recording of the SER spectra of the liposomes in aqueous environment, thus demonstrating the plasmonic properties of the hybrids.