19 research outputs found
PEGylated Terbium-Based Nanorods as Multimodal Bioimaging Contrast Agents
Diagnostic imaging strongly relies on the use of contrast agents (CAs). In general terms, current CAs present undesirable side effects that encourage researchers and pharmaceutical companies to continually search for safer and more versatile alternatives. Here, we describe the synthesis and characterization of terbium-based nanorods (TbNRs) as a potential alternative to traditional CAs for magnetic resonance imaging (MRI) and X-ray computed tomography (CT). The paramagnetism and high atomic number of Tb provide TbNRs with both magnetic relaxivity and X-ray attenuation capabilities. After surface functionalization with a polyethylene glycol (PEG)-derived ligand, TbNRs showed high colloidal stability in physiological media. Additionally, toxicity studies conducted in cell cultures and zebrafish embryos demonstrated the safety of the as-synthesized TbNRs, thus supporting their potential use as CAs. Lastly, in vivo imaging experiments in mice demonstrated that TbNRs produce remarkable contrast enhancement on both MRI and CT.The authors want to express special thanks to Alejandro
DomĂnguez for his invaluable help with the in vivo toxicity
experiments. The authors also thank Dr. Juan F. LĂłpez for his support with the TEM experiments, Dr. InÌaki Orue for VSM measurement, Dr. John Pearson and Luisa MacĂas for assistance with the cell experiments and helpful discussion, Reyes Molina for assistance with animal experiments, and Maria Somoza for helping with the MRI experiments. Authors thank BIONANDâs Nanoimaging Unit. Optical microscopy, TEM, CT, and MRI experiments have been performed in the ICTS âNANBIOSISâ, more specifically in the U28 Unit at BIONAND.Funding for open access charge: Universidad de MĂĄlaga / CBUA. The authors want to express special thanks to Alejandro DomĂnguez for his invaluable help with the in vivo toxicity experiments. The authors also thank Dr. Juan F. LĂłpez for his support with the TEM experiments, Dr. InÌaki Orue for VSM measurement, Dr. John Pearson and Luisa MacĂas for assistance with the cell experiments and helpful discussion, Reyes Molina for assistance with animal experiments, and Maria Somoza for helping with the MRI experiments. Authors thank BIONANDâs Nanoimaging Unit. Optical microscopy,
TEM, CT, and MRI experiments have been performed in the ICTS âNANBIOSISâ, more specifically in the U28 Unit at BIONAND
Controlled Release of Doxorubicin Loaded within Magnetic Thermo-responsive Nanocarriers under Magnetic and Thermal Actuation in a Microfluidic Channel
We report a procedure to grow thermo-responsive polymer shells at the surface of magnetic nanocarriers made of multiple iron oxide superparamagnetic nanoparticles embedded in poly(maleic anhydride-alt-1-ocatadecene) polymer nanobeads. Depending on the comonomers and on their relative composition, tunable phase transition temperatures in the range between 26 and 47 °C under physiological conditions could be achieved. Using a suitable microfluidic platform combining magnetic nanostructures and channels mimicking capillaries of the circulatory system, we demonstrate that thermo-responsive nanobeads are suitable for localized drug delivery with combined thermal and magnetic activation. Below the critical temperature nanobeads are stable in suspension, retain their cargo, and cannot be easily trapped by magnetic fields. Increasing the temperature above the critical temperature causes the aggregation of nanobeads, forming clusters with a magnetic moment high enough to permit their capture by suitable magnetic g..
"Nanohybrids" based on pH-responsive hydrogels and inorganic nanoparticles for drug delivery and sensor applications.
Allyl-PEG capped inorganic NPs, including magnetic iron oxide (IONPs), fluorescent CdSe/ZnS quantum dots (QDs), and metallic gold (AuNPs of 5 and 10 nm) both individually and in combination, were covalently attached to pH-responsive poly(2-vinylpyridine-co-divinylbenzene) nanogels via a facile and robust one-step surfactant-free emulsion polymerization procedure. Control of the NPs associated to the nanogels was achieved by the late injection of the NPs to the polymerization solution at a stage when just polymeric radicals were present. Remarkably, by varying the total amount of NPs injected, the swelling behavior could be affected. Furthermore, the magnetic response as well as the optical features of the nanogels containing either IONPs or QDs could be modified. In addition, a radical quenching in case of gold nanoparticles was observed, thus affecting the final nanogel geometry
"Nanohybrids" based on pH-responsive hydrogels and inorganic nanoparticles for drug delivery and sensor applications
Allyl-PEG capped inorganic NPs, including magnetic iron oxide (IONPs), fluorescent CdSe/ZnS quantum dots (QDs), and metallic gold (AuNPs of 5 and 10 nm) both individually and in combination, were covalently attached to pH-responsive poly(2-vinylpyridine-co-divinylbenzene) nanogels via a facile and robust one-step surfactant-free emulsion polymerization procedure. Control of the NPs associated to the nanogels was achieved by the late injection of the NPs to the polymerization solution at a stage when just polymeric radicals were present. Remarkably, by varying the total amount of NPs injected, the swelling behavior could be affected. Furthermore, the magnetic response as well as the optical features of the nanogels containing either IONPs or QDs could be modified. In addition, a radical quenching in case of gold nanoparticles was observed, thus affecting the final nanogel geometry
Long-circulating PEGylated manganese ferrite nanoparticles for MRI-based molecular imaging
Magnetic resonance based molecular imaging has emerged as a very promising technique for early detection and treatment of a wide variety of diseases, including cancer, neurodegenerative disorders, and vascular diseases. The limited sensitivity and specificity of conventional MRI are being overcome by the development of a new generation of contrast agents, using nanotechnology approaches, with improved magnetic and biological properties. In particular, for molecular imaging, high specificity, high sensitivity, and long blood circulation times are required. Furthermore, the lack of toxicity and immunogenicity together with low-cost scalable production are also necessary to get them into the clinics. In this work, we describe a facile, robust and cost-effective ligand-exchange method to synthesize dual T1 and T2 MRI contrast agents with long circulation times. These contrast agents are based on manganese ferrite nanoparticles (MNPs) between 6 and 14 nm in size covered by a 3 kDa polyethylene glycol (PEG) shell that leads to a great stability in aqueous media with high crystallinity and magnetization values, thus retaining the magnetic properties of the uncovered MNPs. Moreover, the PEGylated MNPs have shown different relaxivities depending on their size and the magnetic field applied. Thus, the 6 nm PEGylated MNPs are characterized by a low r2/r1 ratio of 4.9 at 1.5 T, hence resulting in good dual T1 and T2 contrast agents under low magnetic fields, whereas the 14 nm MNPs behave as excellent T2 contrast agents under high magnetic fields (r2 = 335.6 mM-1 s-1). The polymer core shell of the PEGylated MNPs minimizes their cytotoxicity, and allows long blood circulation times. This combination of cellular compatibility and excellent T2 and r2/r1 values under low magnetic fields, together with long circulation times, make these nanomaterials very promising contrast agents for molecular imaging.Financial support was provided by the Andalusian Ministry of
Health (PI2013-0559 to MPL), Carlos III Institute of Health of
Spain (Spanish Ministry of Economy and Competitiveness)
according to the âStrategic Action in Healthâ (PI14-01600 to DP)
with co-funding by FEDER funds, the Andalusian Ministry of
Economy, Science and Innovation (P10-CTS-6928 and P11-
CTS-8161 to DP), the PAIDI Program from the Andalusian
Government (CTS-677 to DP), the Spanish Ministry of Economy and Competitiveness (MAT2011-26851-CO2-01 to
JMF) and the European Research Council (ERC-StG-2009-
239931 to JMF). MPL thanks to the Andalusian Mobility
Research Program for Nanomedicine (FundaciĂłn PĂșblica
Andaluza Progreso y Salud; Andalusian Ministry of Health)
and the Talentia Postdoctoral Fellowship Program (grant agreement
267226; Andalusian Knowledge Agency; Andalusian
Regional Ministry of Economy, Innovation, Science and
Employment) for the Postdoctoral Fellowships.Peer Reviewe
Long-circulating PEGylated manganese ferrite nanoparticles for MRI-based molecular imaging
Magnetic resonance based molecular imaging has emerged as a very promising technique for early detection and treatment of a wide variety of diseases, including cancer, neurodegenerative disorders, and vascular diseases. The limited sensitivity and specificity of conventional MRI are being overcome by the development of a new generation of contrast agents, using nanotechnology approaches, with improved magnetic and biological properties. In particular, for molecular imaging, high specificity, high sensitivity, and long blood circulation times are required. Furthermore, the lack of toxicity and immunogenicity together with low-cost scalable production are also necessary to get them into the clinics. In this work, we describe a facile, robust and cost-effective ligand-exchange method to synthesize dual T1 and T2 MRI contrast agents with long circulation times. These contrast agents are based on manganese ferrite nanoparticles (MNPs) between 6 and 14 nm in size covered by a 3 kDa polyethylene glycol (PEG) shell that leads to a great stability in aqueous media with high crystallinity and magnetization values, thus retaining the magnetic properties of the uncovered MNPs. Moreover, the PEGylated MNPs have shown different relaxivities depending on their size and the magnetic field applied. Thus, the 6 nm PEGylated MNPs are characterized by a low r2/r1 ratio of 4.9 at 1.5 T, hence resulting in good dual T1 and T2 contrast agents under low magnetic fields, whereas the 14 nm MNPs behave as excellent T2 contrast agents under high magnetic fields (r2 = 335.6 mMâ1 sâ1). The polymer core shell of the PEGylated MNPs minimizes their cytotoxicity, and allows long blood circulation times. This combination of cellular compatibility and excellent T2 and r2/r1 values under low magnetic fields, together with long circulation times, make these nanomaterials very promising contrast agents for molecular imaging.Financial support was provided by the Andalusian Ministry of Health (PI2013-0559 to MPL), Carlos III Institute of Health of Spain (Spanish Ministry of Economy and Competitiveness)
according to the âStrategic Action in Healthâ (PI14-01600 to DP) with co-funding by FEDER funds, the Andalusian Ministry of Economy, Science and Innovation (P10-CTS-6928 and P11-
CTS-8161 to DP), the PAIDI Program from the Andalusian Government (CTS-677 to DP), the Spanish Ministry of Economy and Competitiveness (MAT2011-26851-CO2-01 to
JMF) and the European Research Council (ERC-StG-2009-239931 to JMF). MPL thanks to the Andalusian Mobility Research Program for Nanomedicine (FundaciĂłn PĂșblica Andaluza Progreso y Salud; Andalusian Ministry of Health) and the Talentia Postdoctoral Fellowship Program (grant agreement 267226; Andalusian Knowledge Agency; Andalusian Regional Ministry of Economy, Innovation, Science and Employment) for the Postdoctoral Fellowships.Peer reviewe
Synthesis of 1D-glyconanomaterials by a hybrid noncovalentâcovalent functionalization of single wall carbon nanotubes: a study of their selective interactions with lectins and with live cells
To take full advantage of the remarkable applications of carbon nanotubes in diïŹerent ïŹelds, there is a need to develop eïŹective methods to improve their water dispersion and biocompatibility while maintain- ing their physical properties. In this sense, current approaches suïŹer from serious drawbacks such as loss of electronic structure together with low surface coverage in the case of covalent functionalizations, or instability of the dynamic hybrids obtained by non-covalent functionalizations. In the present work, we examined the molecular basis of an original strategy that combines the advantages of both functionaliza- tions without their main drawbacks. The hierarchical self-assembly of diacetylenic-based neoglycolipids into highly organized and compacted rings around the nanotubes, followed by photopolymerization leads to the formation of nanotubes covered with glyconanorings with a shish kebab-type topology exposing the carbohydrate ligands to the water phase in a multivalent fashion. The glyconanotubes obtained are fully functional, and able to establish speciïŹc interactions with their cognate receptors. In fact, by taking advantage of this selective binding, an easy method to sense lectins as a working model of toxin detection was developed based on a simple analysis of TEM images. Remarkably, diïŹerent experimental settings to assess cell membrane integrity, cell growth kinetics and cell cycle demonstrated the cellular biocompatibility of the sugar-coated carbon nanotubes compared to pristine single-walled carbon nanotubes.ConsejerĂa de EconomĂa, Ciencia e InnovaciĂłn P10-CTS-6928 y P11- CTS-8161 to DP; P07-FQM-2774 to NK, P11-FQM-8046 to IFPAIDI Junta de AndalucĂa CTS-677 to DP; FQM-102 to IFMinisterio de EconomĂa y Competitividad CTQ2013-49066-C2-1-R to NK y PI14-1600 to D
Long-circulating PEGylated manganese ferrite nanoparticles for MRI-based molecular imaging
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Multifunctional Magnetic and Upconverting Nanobeads as Dual Modal Imaging Tools.
We report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. The UCNPs maintain photoluminescent properties even when embedded with the MNPs into the polymer bead. Moreover, the light emitted by the magnetic and upconverting nanobeads (MUCNBs) under NIR excitation (λexc = 980 nm) was clearly observed through different thicknesses of agarose gel or through a mouse skin layer. The comparison with magnetic and luminescent nanobeads based on red-emitting quantum dots (QDs) demonstrated that while the QD-based beads show significant autofluorescence background from the skin, the signal obtained by the MUCNBs allows a decrease in this background. In summary, these results indicate that MUCNBs are good magnetic and optical probes for in vivo multimodal imaging sensors
Synthesis and Characterization of Elongated-Shaped Silver Nanoparticles as a Biocompatible Anisotropic SERS Probe for Intracellular Imaging: Theoretical Modeling and Experimental Verification
Progress in the field of biocompatible SERS nanoparticles has promising prospects for biomedical applications. In this work, we have developed a biocompatible Raman probe by combining anisotropic silver nanoparticles with the dye rhodamine 6G followed by subsequent coating with bovine serum albumin. This nanosystem presents strong SERS capabilities in the near infrared (NIR) with a very high (2.7 Ă 107) analytical enhancement factor. Theoretical calculations reveal the effects of the electromagnetic and chemical mechanisms in the observed SERS effect for this nanosystem. Finite element method (FEM) calculations showed a considerable near field enhancement in NIR. Using density functional quantum chemical calculations, the chemical enhancement mechanism of rhodamine 6G by interaction with the nanoparticles was probed, allowing us to calculate spectra that closely reproduce the experimental results. The nanosystem was tested in cell culture experiments, showing cell internalization and also proving to be completely biocompatible, as no cell death was observed. Using a NIR laser, SERS signals could be detected even from inside cells, proving the applicability of this nanosystem as a biocompatible SERS probe