A metal atom cluster-embedded magnetic iron oxide nanoparticle (MION) is disclosed. The metal atom cluster is embedded in an iron oxide crystal matrix and has a content of 0.1% to 15%. A method for preparing the MION includes: dissolving a metal precursor of iron oxide, an organic acid, and an organic amine in an organic solvent to form a uniform reaction system; heating the reaction system to 150° C. to 350° C. in an inert gas atmosphere; adding a metal atom cluster precursor; and heating to perform a reflux reaction until the metal atom cluster precursor is completely decomposed. The MION shows improved magnetic properties due to the embedding of the metal atom cluster, and the iron oxide fully ensures the stability of properties of the nanoparticles. The nanoparticles are especially applicable to biomedical detection and therapy and other fields.

The present invention provides a nanoparticle including at least one poly(vinyl alcohol) (PVA) having a molecular weight of from about 10 kDa to about 200 kDa, substituted with one or more moieties selected from: a therapeutic agent having a boronic acid moiety, wherein the therapeutic agent is covalently linked to the PVA via a boronate ester bond; a crosslinking group having a disulfide moiety, wherein the crosslinking group is covalently linked to the PVA, and a porphyrin, wherein the porphyrin is covalently linked to the PVA. Use of the nanoparticles for tumor detection and the treatment of diseases, including methods for photodynamic therapy and photothermal therapy, are also described.

A system and method are provided for tracking magnetically-labeled substances, such as transplanted cells, in subjects using magnetic resonance imaging (MRI). The method includes obtaining a quantity of a substance that comprises an MRI contrast compound or is otherwise magnetically-labeled for purposes of an MRI scan, administering the substance into a region of interest of a subject, performing an imaging scan of a portion of the subject comprising the region of interest, obtaining an imaging data set from the scan, reducing the dataset into pixel groupings based on intensity profiles, where the pixel groupings have a pixel size larger than the expected pixel size of a unit of the MRI contrast compound or magnetically-labeled substance, extracting candidate pixel matrices from the imaging data, training a machine learning (ML) module by using the candidate pixel matrices, quantifying the presence, number and/or location of units of the substance within the subject by using the ML module, and displaying a visual representation of an identification of the substances within the subject as a result of using the ML module.

Disclosed herein are nanoconstructs comprising a nanoparticle, coated with additional agents such as cationic polymers, stabilizers, targeting molecules, labels, oligonucleotides and small molecules. These constructs may be used to deliver compounds to treat solid tumors and to diagnose cancer and other diseases. Further disclosed are methods of making such compounds and use of such compounds to treat or diagnose human disease.

The present invention provides stem cells loaded with bi-functional magnetic nanoparticles (nanoparticle-loaded stem cells (NLSC)) that both: a) heat in an alternating magnetic field (AMF); and b) provide MRI contrast enhancement for MR-guided hyperthermia. The nanoparticles in the NLSC are non-toxic, and do not alter stem cell proliferation and differentiation, the nanoparticles do however, become heated in an alternating magnetic field, enabling therapeutic applications for cancer treatment. Due to the fact that circulating stem cells home to tumors and metastasis, and participate in neovascularization of growing tumors, the NLSC of the present invention allows tracking of the tissue distribution of infused stem cells and selective heating of targeted tissues with AMF. NLSC can deliver hyperthermia to hypoxic areas in tumors for sensitization of those areas to subsequent treatment, thus delivering therapy to the most treatment-resistant tumor regions. The heating of diseased tissue either results in direct cell killing or makes the tumor more susceptible to radio- and/or chemotherapy. The targeted hyperthermia provided by the present invention has clinical potential because it is associated with fewer side effects, and can also be used in combination with conventional treatment modalities, significantly enhancing their effectiveness. The NLSC of the present invention can be used for MR image-guided hyperthermia in oncology, in stem cell research for cell tracking and heating, and for elimination of mis-injected stem cells.

Various embodiments are directed to color-coded and size-calibrated polymeric particles comprising an acrylate-based hydrogel core incorporating one or more chromophores of interest, and an outer shell comprising polyphosphazenes of formula I, useful for various therapeutic and/or diagnostic procedures. In various embodiments, the color-coded and size-calibrated polymeric particles can be employed in any particle-mediated procedure, including as embolic agents, dermal fillers, and various implantable devices for a broad range of clinical and cosmetic applications. The incorporation of a particular chromophore formulation that correlates with a pre-determined size specificity for implantable and loadable polymeric particles (“color-coded and size-calibrated”) enables the visual detection and identification of particles exhibiting a particular size of interest, and minimizes the probability of user-introduced or procedural errors.

Systems, methods and related devices used to produce and collect polarized noble gas to inhibit, suppress, detect or filter alkali metal nanoclusters to preserve or increase a polarization level thereof. The systems can include a pre-sat chamber that has an Area Ratio between 20 and 500.

Systems, methods and related devices used to produce and collect polarized noble gas to inhibit, suppress, detect or filter alkali metal nanoclusters to preserve or increase a polarization level thereof. The systems can include a pre-sat chamber that has an Area Ratio between 20 and 500.

The invention is directed to the field of gene therapy, i.e. gene delivery into target cells, tissue, organ and organism, and more particularly to gene delivery via viral vectors. The inventors showed that it is possible by chemical coupling to modulate the coupling of a ligand in the surface of the capsid of AAV, for example AAV2 and AAV3b. In particular, the present invention relates to a recombinant Adeno-Associated Virus (rAAV) vector particle having at least one primary amino group contained in the capsid proteins, chemically coupled with at least one ligand L, wherein coupling of said ligand L is implemented through a bond comprising a —CSNH— bond and an optionally substituted aromatic moiety.

Particularly, the inventors tested the chemical coupling of mannose ligand on AAV2 for subretinally injection to rats. The present invention further relates to a method for chemically coupling an Adeno-Associated Virus (AAV) vector particle with at least one ligand L and to a Recombinant Adeno-Associated Virus (rAAV) vector particle obtained by said method as well as a pharmaceutical composition comprising it and their corresponding medical use.

The instant application describes improved methods and compositions for the systemic delivery of therapeutic exosomes to a subject in need thereof. In certain embodiments, the current invention reduces the amount of exosomes delivered to liver, spleen and combinations thereof to allow greater distribution to other areas of the body such as, but not limited to, the brain, pancreas, lung, kidney, muscle. In certain embodiments, the methods involve the injection of one or multiple doses of non-therapeutic exosomes prior to the injection of a suitable therapeutic dose of exosomes with a therapeutic payload. Also included are methods to improve immune clearance of exosomes in subjects by inhibiting phagocytosis.