The present invention relates to the field of diagnostics and, more in particular, to MRI activatable contrast agents and compositions thereof for the detection of nuclease activity, wherein said nuclease activity is caused by microbial infection or by nuclease activity related to cancer, particularly colon cancer or pancreatic cancer. Activatable contrast agents for MRI have been developed, wherein the oligonucleotide is flanked by a paramagnetic and a superparamagnetic agent, and thus providing magnetic quenching. Moreover, the oligonucleotide has regions that confer resistance to mammalian endonucleases and sensitivity to microbial endonucleases. When the activatable contrast agent of the invention is in the presence of microbial nuclease activity or a tumour cell nuclease activity, the oligonucleotide is cleaved, agents are unquenched, and the signal derived from the activated contrast agent is detected by MRI.

The present invention is directed generally to eukaryotic cells comprising single-celled organisms that are introduced into the eukaryotic cell through human intervention and which transfer to daughter cells of the eukaryotic cell, and methods of introducing such single-celled organisms into eukaryotic cells. The invention provides single-celled organisms that introduce a phenotype to eukaryotic cells that is maintained in daughter cells. The invention additionally provides eukaryotic cells containing magnetic bacteria. The invention further provides eukaryotic cells engineered with single-celled organisms to allow for multimodal observation of the eukaryotic cells. Each imaging method (or modality) allows the visualization of different aspects of anatomy and physiology, and combining these allows the imager to learn more about the subject being imaged.

The present invention relates to an isolated antibody, which selectively binds to CLEC14A, wherein said antibody (a) comprises at least one heavy chain variable region that comprises three CDRs and at least one light chain variable region that comprises three CDRs, wherein said heavy chain variable region comprises: (i) a variable heavy (VH) CDR1 that has the amino acid sequence of SEQ ID NO. 105, preferably of SEQ ID NO: 2 or 42; (ii) a VH CDR2 that has the amino acid sequence of SEQ ID NO. 106, preferably of SEQ ID NO: 3 or 43; and/or (iii) a VH CDR3 that has the amino acid sequence of SEQ ID NO. 107, preferably of SEQ ID NO: 4 or 44; and/or wherein said light chain variable region comprises: (iv) a variable light (VL) CDR1 that has the amino acid sequence of SEQ ID NO. 108, preferably of SEQ ID NO: 6 or 46; (v) a VL CDR2 that has the amino acid sequence of SEQ ID NO. 109, preferably of SEQ ID NO: 7 or 47; and/or (vi) a VL CDR3 that has the amino acid sequence of SEQ ID NO. 1 10, preferably of SEQ ID NO: 8 or 48; or (b) comprises at least one heavy chain variable region that comprises three CDRs and at least one light chain variable region that comprises three CDRs, wherein said heavy chain variable region comprises: (i) a variable heavy (VH) CDR1 that has the amino acid sequence of SEQ ID NO: 22; (ii) a VH CDR2 that has the amino acid sequence of SEQ ID NO: 23; and/or (iii) a VH CDR3 that has the amino acid sequence of SEQ ID NO: 24; and/or wherein said light chain variable region comprises: (iv) a variable light (VL) CDR1 that has the amino acid sequence of SEQ ID NO: 26; (v) a VL CDR2 that has the amino acid sequence of SEQ ID NO: 27; and/or (vi) a VL CDR3 that has the amino acid sequence of SEQ ID NO: 28; or (c) is an antibody which can compete with antibody (a) or (b) for binding to CLEC14A. The invention further provides chimeric antigen receptors, nucleic acid molecules encoding the antibodies of the invention or the chimeric antigen receptors, vectors, cells and methods/uses of the antibodies and chimeric antigen receptors.

Silica nanocarriers hybridized with superparamagnetic iron oxide nanoparticles (“SPIONs”) and curcumin through equilibrium or enforced adsorption technique. Methods for dual delivery of SPIONs and curcumin to a target for diagnosis or therapy, for example, for SPION-based magnetic resonance imaging or for targeted delivery of curcumin to a cell or tissue. The technique can be extend to co-precipitation of mixed metal oxide involving Ni, Mn, Co and Cu oxide. The calcination temperature can be varied from 500-900° C. The nanocombination is functionalized with chitosan, polyacrylic acid, PLGA or another agent to increase its biocompatibility in vivo.

Silica nanocarriers hybridized with superparamagnetic iron oxide nanoparticles (“SPIONs”) and curcumin through equilibrium or enforced adsorption technique. Methods for dual delivery of SPIONs and curcumin to a target for diagnosis or therapy, for example, for SPION-based magnetic resonance imaging or for targeted delivery of curcumin to a cell or tissue. The technique can be extend to co-precipitation of mixed metal oxide involving Ni, Mn, Co and Cu oxide. The calcination temperature can be varied from 500-900° C. The nanocombination is functionalized with chitosan, polyacrylic acid, PLGA or another agent to increase its biocompatibility in vivo.

Fibroblast activation protein (FAP)-targeting compounds (e.g., conjugates); a method for imaging cancer or fibrosis; and methods for treating an inflammatory disease/disorder and cancer.

Described herein are particles comprising a crystalline matrix and a dopant, wherein one of the atoms of the matrix is .sup.19F and .sup.31P, or .sup.13C, .sup.15N, .sup.29Si, .sup.16O, .sup.17O, .sup.23Na, .sup.39K, .sup.25Mg, .sup.40Ca, .sup.43Ca or deuterium; and the dopant is a compound involved in a biological process in a mammalian organism; and wherein the dopant is present in an amount of between 0.01% and 20% of the plurality of particles, and wherein when the matrix comprises an atom selected from the group of .sup.13C, .sup.15N, .sup.29Si, .sup.16O, .sup.17O, .sup.23Na, .sup.39K, .sup.25Mg, .sup.40Ca, .sup.43Ca and deuterium, and the dopant is isotopically enriched.

The invention relates to a method for synthesizing ultrasmall silica nanoparticles, useful in particular for diagnostics and/or therapy. More specifically, a method for synthesizing silica nanoparticles, said method comprising the mixing of at least one silane which is negatively charged at physiological pH with at least one silane which is neutral at physiological pH, and/or at least one silane which is positively charged at physiological pH, wherein: —the molar ratio A of neutral silane(s) to negatively charged silane(s) is defined as follows: 0≤A≤6, —the molar ratio B of positively charged silane(s) to negatively charged silane(s) is defined as follows: 0≤B≤5, —the molar ratio C of neutral and positively charged silanes to negatively charged silane(s) is defined as follows: 0<C≤8. The invention also relates to the obtained ultrasmall silica nanoparticles.

The invention relates to a method for synthesizing ultrasmall silica nanoparticles, useful in particular for diagnostics and/or therapy. More specifically, a method for synthesizing silica nanoparticles, said method comprising the mixing of at least one silane which is negatively charged at physiological pH with at least one silane which is neutral at physiological pH, and/or at least one silane which is positively charged at physiological pH, wherein: —the molar ratio A of neutral silane(s) to negatively charged silane(s) is defined as follows: 0≤A≤6, —the molar ratio B of positively charged silane(s) to negatively charged silane(s) is defined as follows: 0≤B≤5, —the molar ratio C of neutral and positively charged silanes to negatively charged silane(s) is defined as follows: 0<C≤8. The invention also relates to the obtained ultrasmall silica nanoparticles.

Silica nanocarriers hybridized with superparamagnetic iron oxide nanoparticles (“SPIONs”) and curcumin through equilibrium or enforced adsorption technique. Methods for dual delivery of SPIONs and curcumin to a target for diagnosis or therapy, for example, for SPION-based magnetic resonance imaging or for targeted delivery of curcumin to a cell or tissue. The technique can be extend to co-precipitation of mixed metal oxide involving Ni, Mn, Co and Cu oxide. The calcination temperature can be varied from 500-900° C. The nanocombination is functionalized with chitosan, polyacrylic acid, PLGA or another agent to increase its biocompatibility in vivo.