Provided herein are protein contrast agents and targeted protein contrast agents, formulations thereof, and methods of use, including but not limited to, as a magnetic resonance imaging contrast agent.

Provided are macrocyclic compounds and compounds with two or more macrocyclic groups, iron coordinated macrocyclic compounds, and iron coordinated compounds with two or more macrocyclic groups. The iron is high-spin iron(III). The iron coordinated compounds may exhibit a negative redox potential (e.g., relative to a normal hydrogen electrode at a biologically relevant pH, for example, a pH of 6.5-7.5). The compounds can be used as MRI contrast agents.

The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.

The present invention relates to an efficient method for grafting a properties-imparting compound onto a polymeric substrate containing carbon-hydrogen (C—H) bonds using clip chemistry. The method of the invention includes coating the substrate with the properties-imparting compound and irradiating it with a reactive light source, and repeating this sequence at least once. The present invention further relates to surface-modified polymeric substrates grafted with a properties-imparting compound, in particular obtained with the method of the invention, medical devices comprising same, and non-medical of said surface-modified polymeric substrates.

The present invention relates to an efficient method for grafting a properties-imparting compound onto a polymeric substrate containing carbon-hydrogen (C—H) bonds using clip chemistry. The method of the invention includes coating the substrate with the properties-imparting compound and irradiating it with a reactive light source, and repeating this sequence at least once. The present invention further relates to surface-modified polymeric substrates grafted with a properties-imparting compound, in particular obtained with the method of the invention, medical devices comprising same, and non-medical of said surface-modified polymeric substrates.

The disclosure relates to methods for treating tumors. In particular, the disclosure relates to a method of treating a tumor by ionizing radiations in a subject in need thereof, said method comprising the steps of: (i) injecting a first therapeutically effective amount of high-Z element containing nanoparticles as radiosensitizing agents in said subject in need thereof within a period between 2 and 7 days prior to the first irradiation of the tumor, (ii) injecting a second therapeutically effective amount of the same or different high-Z element containing nanoparticles within a period between 1 hour to 12 hours prior to the first irradiation of the tumor, and, (iii) irradiating the tumor of said subject with a therapeutically efficient dose of radiations;
wherein said high-Z element containing nanoparticles are nanoparticles containing an element with an atomic Z number higher than 40 and said nanoparticles have a mean hydrodynamic diameter below 10 nm.

The disclosure relates to methods for treating tumors. In particular, the disclosure relates to a method of treating a tumor by ionizing radiations in a subject in need thereof, said method comprising the steps of: (i) injecting a first therapeutically effective amount of high-Z element containing nanoparticles as radiosensitizing agents in said subject in need thereof within a period between 2 and 7 days prior to the first irradiation of the tumor, (ii) injecting a second therapeutically effective amount of the same or different high-Z element containing nanoparticles within a period between 1 hour to 12 hours prior to the first irradiation of the tumor, and, (iii) irradiating the tumor of said subject with a therapeutically efficient dose of radiations;
wherein said high-Z element containing nanoparticles are nanoparticles containing an element with an atomic Z number higher than 40 and said nanoparticles have a mean hydrodynamic diameter below 10 nm.

A process for the preparation of beads including a biocompatible hydrophobic polymer, a perfluorocarbon, polyvinylalcohol and optionally a metal compound, including the steps of: adding the perfluorocarbon and optionally the metal compound to a solution of the biocompatible hydrophobic polymer in a polar solvent to provide a first liquid mixture, adding the first liquid mixture to an aqueous solution of a biocompatible surfactant including polyvinylalcohol under sonication to obtain a second liquid mixture, a) maintaining the sonication of the second liquid mixture while cooling, b) evaporating the polar solvent from the second liquid mixture to obtain a suspension of beads including the biocompatible hydrophobic polymer, the perfluorocarbon and optionally the metal compound, c) separating the beads from the suspension and preparing a water suspension of the beads and d) freeze-drying the water suspension to obtain the beads, wherein the addition of the first liquid mixture to the biocompatible surfactant in step b) is performed within a period of at most 10 seconds, wherein the sonication in step b) and the sonication in step c) are performed directly into the liquid mixtures by for example a probe or flow sonicator at an amplitude of at least 120 μm for 0.01-10 minutes and wherein the weight ratio of the biocompatible surfactant to the biocompatible hydrophobic polymer is at least 3:1. Beads having close F—H2O interactions, which are suitable for imaging purposes.

A biocompatible magnetic material containing an iron oxide nanoparticle and one or more biocompatible polymers, each having formula (I) below, covalently bonded to the iron oxide nanoparticle:

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in which each of variables R, L, x, and y is defined herein, the biocompatible magnetic material contains 4-15% Fe(II) ions relative to the total iron ions. Also disclosed in a method of preparing the biocompatible magnetic material.

Nanoparticle compositions for delivery of nucleic acids to subjects including modified dendrimers comprising cores, one or more of homogeneous or heterogeneous intermediate and terminal layers, and therapeutic or immunogenic nucleic acid agents enclosed within nanop article compositions are described. Methods for treating or preventing diseases or conditions in a subject by administering the nanoparticle compositions that provide immune responses and synergistic therapeutic or preventive effects are provided.