ABSTRACT
Molecules that undergo activation or modulation following the addition of benign external small-molecule chemical stimuli have numerous applications. Here, we report the highly efficient "decaging" of a variety of moieties by activation of a "self-immolative" linker, by application of water-soluble and stable tetrazine, including the controlled delivery of doxorubicin in a cellular context.
Subject(s)
Drug Carriers/chemistry , Heterocyclic Compounds, 1-Ring/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cycloaddition Reaction , Doxorubicin/chemistry , Doxorubicin/metabolism , Doxorubicin/toxicity , Drug Liberation , HEK293 Cells , Humans , Nanoparticles/chemistry , Polyethylene Glycols/chemistryABSTRACT
Protein cages have well-defined structures and can be chemically and biologically engineered in many ways, making them useful platforms for drug delivery applications. Taking advantage of the unique structure feature of apoferritin, a new theranostic nanocarrier is proposed herein. The apoferritin protein is effective for the encapsulation of maghemite nanoparticles and for loading a significant dose of doxorubicin (DOX) drug. This simultaneous loading of maghemite nanoparticles and DOX has been achieved using either co-encapsulation or surface-binding approaches. Maghemite nanoparticles coated with the protein apoferritin are an effective long-term MRI liver contrast agent and we report here that additionally they can serve as an anticancer drug-delivery system. In particular we show that maghemite-containing apoferritin can sustain the DOX delivery under period of 10 to 25 days depending on the environmental conditions.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Ferric Compounds/chemistry , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Microscopy, Electron, TransmissionABSTRACT
We have developed a simple process to fabricate on a bioplatform patterns of nanoparticles of a molecule-based magnet. Nanoparticles of the ferromagnetic Prussian blue derivative CsxNi[Cr(CN)6] were orderly deposited onto S-layers of Lysinibacillus sphaericus, forming a dense carpet of nanoparticles following the square lattice (p4) pattern of the biotemplate. These results are encouraging to extend this approach by focusing on molecule-based magnets patterned into domains with controlled shapes and positions on a biosurface.
Subject(s)
Bacillus/cytology , Chromium/chemistry , Ferrocyanides/chemistry , Magnetite Nanoparticles/chemistry , Magnets/chemistry , Nickel/chemistry , Magnetite Nanoparticles/ultrastructure , Nanotechnology/methodsABSTRACT
New long-circulating maghemite nanoparticles of 4 and 6 nm, coated with an apoferritin protein capsid, exhibit useful properties to act as magnetic resonance imaging (MRI) contrast agents. A full in vivo study of the so-called apomaghemites reveals that their long-term MRI properties are better than those of a standard superparamagnetic iron oxide (SPIO) widely used in biomedical applications. The biodistribution of apomaghemites and standard SPIO was investigated by MRI in mice at two different concentrations, 6 and 2.5 mg of Fe·kg(-1), over 60 days. Significant differences are found at low dose (2.5 mg of Fe·kg(-1)). Thus, whereas apomaghemites are active for MR bioimaging of liver for 45 days, standard SPIO is not effective beyond 7 days. On the basis of our data, we may concluded that apomaghemites can act as new long-term MRI liver contrast agents, allowing first the diagnosis of a liver pathology and then monitoring after treatment without the need for a second injection.
Subject(s)
Apoferritins , Contrast Media , Magnetic Resonance Imaging/methods , Magnetite Nanoparticles , Nanoparticles , Animals , Liver/metabolism , Mice , Mice, Inbred BALB C , Tissue DistributionABSTRACT
Ferritin (Ft) interaction with the Zn-complexes of mammalian MT1, MT2 and MT3 metallothioneins (MT) leads to simultaneous Fe(II) and Zn(II) release.
Subject(s)
Ferritins/chemistry , Iron/chemistry , Metallothionein/chemistry , Zinc/chemistry , Oxidation-ReductionABSTRACT
A new approach for the preparation of carbohydrate-coated magnetic nanoparticles is reported. In a first step, we show that the pH-driven assembly-disassembly natural process that occurs in apoferritin protein is effective for the encapsulation of maghemite nanoparticles of different sizes: 4 and 6 nm. In a second step, we demonstrate that the presence of functional amine groups in the outer shell of apoferritin allows functionalization with two carbohydrates, N-acetyl-D-glucosamine and d-mannose. High-resolution electron microscopy (HREM), high angle annular dark field scanning electron microscopy (HAADF-STEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), and SQUID technique have been used to characterize the magnetic samples, termed herein Apomaghemites. The in vivo magnetic resonance imaging (MRI) studies showed the efficiency in contrasting images for these samples; that is, the r(2) NMR relaxivities are comparable with Endorem (a commercial superparamagnetic MRI contrast agent). The r(2) relaxivity values as well as the pre-contrast and post-contrast T(2)*-weighted images suggested that our systems could be used as perspective superparamagnetic contrast agents for magnetic resonance imaging (MRI). The carbohydrate-functionalized Apomaghemite nanoparticles retained their recognition abilities, as demonstrated by the strong affinity with their corresponding carbohydrate-binding lectins.
Subject(s)
Apoferritins/chemistry , Ferric Compounds/chemistry , Lectins/chemistry , Magnetics , Nanoparticles/chemistry , Protein Subunits/chemistry , Carbohydrates/chemistry , Crystallography, X-Ray , Hydrogen-Ion Concentration , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Models, Molecular , Particle Size , Surface PropertiesABSTRACT
Pd nanoparticles exhibiting permanent magnetism at room temperature have been prepared within the apoferritin cavity. Pd nanoparticles in air and under an inert atmosphere were synthesized to study the influence of the aerobic and anaerobic conditions in the final magnetic properties. The surface of nanoparticles as well as the type of crystalline phase could determine the magnetic properties. X-ray powder diffraction, including Debye-function analysis, transmission electronic microscopy, and magnetization measurements have been used for characterizing the nanoparticles.
Subject(s)
Apoferritins/chemistry , Magnetics , Nanoparticles/chemistry , Palladium/chemistry , Models, Chemical , Nanoparticles/ultrastructure , Temperature , X-Ray DiffractionABSTRACT
Bimetallic CoNi nanoparticles have been prepared within the apoferritin cavity. The protein shell controls size, prevents aggregation, and makes nanoparticles water-soluble. The CoNi series prepared in this way were structurally and magnetically characterized, the resulting magnetic properties varying accordingly with composition (Co(75)/Ni(25), Co(50)/Ni(50), Co(25)/Ni(75)). Co and Ni metals were associated in each nanoparticle, as demonstrated by high-angle annular dark field scanning electron microscopy and electron energy loss spectroscopy (EELS). After intentional oxidation, the CoNi nanoparticles were characterized by EELS, X-ray absorption near edge structure (XANES), and SQUID measurements to evaluate the importance of the oxidation on magnetic properties.
Subject(s)
Apoferritins/chemistry , Cobalt/chemistry , Lithium/chemistry , Magnetics/methods , Metal Nanoparticles/chemistry , Nanotechnology/methods , Nickel/chemistry , Catalysis , Crystallization , Electric Conductivity , Electrochemistry/methods , Microscopy, Electron, Transmission/methods , Nanostructures , Oxidation-Reduction , Particle Size , Surface Properties , Water/chemistry , X-Ray DiffractionABSTRACT
We have prepared water-soluble gadolinium oxide nanoparticles that show potential as MRI contrast agents. The particles were built into the apoferritin cavity and have an average size of 5 nm. After seven days a loss of 5% of Gd was detected compared with the as-prepared samples; after that the Gd remained constant and stabilized inside the apoferritin, indicating that the apoferritin capsid acts as a Gd store, avoiding metal delivery and consequent toxicity. The NMR longitudinal and transverse relaxivities resulted about 10 and 70 times higher than the ones of clinically approved paramagnetic Gd-chelates, thus indicating the possible route for synthesizing a novel class of MRI contrast agents.
