Modified red blood cells (RBCs) including one or more surface proteins or lipids covalently linked to a cargo by click chemistry are provided. In some examples, the cargo is a cancer therapeutic agent, an autoimmune antigen, or an antigen of a bacterial or viral agent. Also provided are methods of treating a subject with a disease or disorder with the modified RBCs or methods of treating a subject with a disease or disorder or performing imaging analysis of a subject, including administering to the subject a composition including an azido-modified sugar moiety, thereby generating red blood cells comprising one or more azido-labeled surface proteins and administering to the subject a composition including a cargo for treating or inhibiting the disease or disorder, wherein the cargo is capable of covalently binding to the one or more azido-labeled surface proteins or lipids.

The present invention relates to the use of a formation agent, such as nitric oxide or sodium nitrite to produce methemoglobin as an alternative MRI contrast agent. The formation agent can be infused using either a respiratory system or a delivery mechanism. One embodiment of this invention relates to systems and methods for producing an image of an internal region with a magnetic resonance scanning system. Blood is drawn from the patient. The blood is exposed to formation agent through a delivery system, to produce blood that has a higher saturation of methemoglobin. Where in vitro techniques are used the treated blood is injected back into the patient. The patient is scanned in the magnetic resonance scanner. These systems and methods can be used to produce images of regions which may not otherwise be possible with other contrasting agents. For example, an accurate vascular brain MRI may not be as informative if the patient is injected with an existing contrasting agent. In addition, an alternate embodiment of the invention relates to internally exposing the blood to the formation agent by placing the gas-permeable membrane along a particular blood pathway or intravenous sodium nitrite.

The invention relates to novel biocompatible hybrid nanoparticles of very small size, useful in particular for diagnostics and/or therapy. The purpose of the invention is to offer novel nanoparticles which are useful in particular as contrast agents in imaging (e.g. MRD and/or in other diagnostic techniques and/or as therapeutic agents, which give better performance than the known nanoparticles of the same type and which combine both a small size (for example less than 20 nm) and a high loading with metals (e.g. rare earths), in particular so as to have, in imaging (e.g. MRI), strong intensification and a correct response (increased relaxivity) at high frequencies. Thus, the nanoparticles according to the invention, with diameter d.sub.1 between 1 and 20 nm, each comprise a polyorganosiloxane (POS) matrix including gadolinium cations optionally associated with doping cations; a chelating graft C.sup.1 DTPABA (diethylenetriaminepentaacetic acid bisanhydride) bound to the POS matrix by an SiC covalent bond, and present in sufficient quantity to be able to complex all the gadolinium cations; and optionally another functionalizing graft Gf* bound to the POS matrix by an SiC covalent bond (where Gf* can be derived from a hydrophilic compound (PEG); from a compound having an active ingredient PA1; from a targeting compound; from a luminescent compound (fluorescein). The method for the production of these nanoparticles and the applications thereof in imaging and in therapy also form part of the invention.

Described herein are particle-driven radiogenomics systems and methods that can be used to identify imaging features for prediction of intratumoral and interstitial nanoparticle distributions in cancers (e.g., in low grade and/or high-grade brain cancers (e.g., gliomas, e.g., primary gliomas)). In certain embodiments, the systems and methods described herein extract and combine quantitative multi-dimensional data generated from structural, functional, and/or metabolic imaging. In certain embodiments, the combined multidimensional data is linked to intratumoral and interstitial nanoparticle distributions. For example, this linked data can be used to determine quantitative functional-metabolic multimodality particle-based imaging features and to predict treatment efficacy. These techniques provide an improved quantitative ability to measure treatment response and determine tumor progressions compared to traditional size-based imaging methods.

In one aspect, the disclosure relates to precipitated hyperpolarized substrates, methods of making the same, contrast agents comprising the same, and methods of diagnosing and/or monitoring the progress of a disease using the same. In one aspect, the method comprises contacting a solution containing a first solvent and a hyperpolarized substrate with a non-polar organic solvent. In a further aspect, the precipitated hyperpolarized substrate can be separated from the first solvent, the non-polar organic solvent, or any combination thereof by filtration. In still another aspect, the method further includes redissolving the precipitated hyperpolarized substrate in a biocompatible solvent such as, for example, water or a physiologically-acceptable buffer. In any of these aspects, hyperpolarization of the substrate can be accomplished using Signal Amplification by Reversible Exchange (SABRE).

A core-shell nanoparticle having a cleaned nitrogen-vacancy nanodiamond (NVND) core surrounded by an upconversion nanoparticle (UCNP) shell, wherein the cleaned nitrogen-vacancy nanodiamond (NVND) core comprises a cleaned nitrogen-vacancy nanodiamond, wherein the UCNP shell comprises an upconversion nanoparticle (UCNP), wherein the UCNP comprises lithium yttrium fluoride (LiYF.sub.4) doped with a lanthanide ion combination, wherein the lanthanide ion combination comprises a M1 ion and a M2 ion, wherein M1 is ytterbium (Yb) or neodymium (Nd) and M2 is erbium (Er), thulium (Tm) or holmium (Ho), and wherein the core-shell nanoparticle emits a red-emission upon a near-infrared (NIR) excitation is disclosed. Integration of cleaned NVNDs with UNCPs for enhancing optical manipulation and enabling efficient energy transfer for applications in biological imaging, quantum sensing and laser cooling is disclosed.

The present invention provides preparations of MSCs with important therapeutic potential. The MSC cells are non-primary cells with an antigen profile comprising less than about 1.25% CD45+ cells (or less than about 0.75% CD45+), at least about 95% CD105+ cells, and at least about 95% CD166+ cells. Optionally, MSCs of the present preparations are isogenic and can be expanded ex vivo and cryo-preserved and thawed, yet maintain a stable and uniform phenotype. Methods are taught here of expanding these MSCs to produce a clinical scale therapeutic preparations and medical uses thereof.

Disclosed is a multi-functional nanoparticle delivery system comprising a biodegradable core of poly(lactic-co-glycolic acid) (PLGA) or calcium phosphate (CaP), encapsulating a nicotinamide adenine dinucleotide (NAD.sup.+) precursor and a sirtuin activator. Surrounding the core is a liposomal or polymeric layer containing one or more senolytic agents, and an outer layer of magnetic iron oxide nanoparticles for targeted delivery, external manipulation, and imaging. In some embodiments, the nanoparticle surface is functionalized for conjugation with autologous mesenchymal stem cells to enhance homing and regenerative potential. The system is pH-responsive, releasing its payload in acidic microenvironments typical of senescent or diseased cells, while remaining stable at physiological pH. This integrated design supports NAD.sup.+ restoration, sirtuin activation, senescent cell clearance, and tissue regeneration. Applications include treatment of age-related diseases, regenerative medicine, cardiovascular and neurodegenerative disorders, and cosmetic skin rejuvenation.

The present disclosure describes formulations, methods, and devices tor biomarker sampling and therapeutic delivery using magnetic formulations. When combined with the application of external magnetic fields, magnetic formulations move within the nasal cavity. Magnetic formulations provide benefits including the ability to: target or steer placement of the formulations via a magnetic field, enhance mixing of the formulation via a magnetic field, enhance biological material collection via antibody-coated magnetic beads, or enhance sample retrieval via a magnetic-tipped inserter. Example biological materials for collection include proteins, enzymes, neural stem cells, and other biomarkers.

The present disclosure presents nanoparticle compositions for use in the treatment, prevention, or imaging of a disease (e.g., cancer), methods of treating, preventing, or imaging a disease in a subject in need thereof with the nanoparticle compositions, and methods of preparing the nanoparticle compositions of the disclosure. The nanoparticle compositions can include a magnetic nanoparticle ferric chloride, ferrous chloride, or a combination thereof, and a dextran coating functionalized with one or more amine groups.