Provided herein are compositions and methods for diagnosis and treatment of early-stage atherosclerotic plaques and reduction of plaques in arteries. In particular, provided herein are high-density-lipoprotein-functionalized magnetic nanostructures (HDL-MNS) capable of (i) precise anatomic detection of atherosclerotic lesions, (ii) removal of excess cholesterol from macrophage cells in atherosclerotic plaque, and/or (iii) delivery of therapeutic agents to plaque locations, and methods of diagnosis and treatment of atherosclerosis.

A method of preparing a coated nanoparticle can include decomposing a compound to produce a nanoparticle, oxidizing the nanoparticle to produce an oxidized nanoparticle, and coating the oxidized nanoparticle with a zwitterionic ligand to produce the coated nanoparticle. The coated nanoparticle or the nanoparticle can be used in magnetic resonance imaging.

Disclosed herein are embodiments of nanoparticle composites that comprise covalently coupled stabilizing agent molecules that improve stability of the nanoparticle composites and allow for tight packing of lipids and/or membranes. The nanoparticle composites can further comprise inhibition inhibitors and/or lipid components that interact to form a hybrid lipid bilayer membrane around the nanoparticle core. The nanoparticle composites can be coupled to drugs, targeting moieties, and imaging moieties. The nanoparticle composites can be used for in vivo drug deliver, disease diagnosis/treatment, and imaging.

A pharmaceutical composition includes a plurality of metal nanoparticles and at least one therapeutic agent. Each of the metal nanoparticles includes a core and a stabilizing agent coated on a surface of the core. The at least one therapeutic agent is attached to the stabilizing agent of the metal nanoparticles. Each of the therapeutic agent is an amphiphilic compound and has at least one hydrophobic chain interacting with the stabilizing agent. The pharmaceutical composition may further include a polymer shell encapsulating the metal nanoparticles and the therapeutic agent for enabling controlled release of the therapeutic agent. The pharmaceutical compositions are bifunctional and may be used for diagnosing and treating cancer. Methods for using the pharmaceutical compositions in conjunction with radiation therapy to diagnose and treat cancer are also provided.

The invention relates to a ligand compound having a structure A-B-C, wherein (a) A represents a mono- or polyphosphorylated amino acid linked to part B by its amino group to form an amide bond; B represents (i) a carboxylic acid, and (ii) an amino acid or peptidyl group of 2-10 amino acids, an alkyl or alkenyl group comprising 1-26 carbon atoms, a polyethylene glycol group comprising 1-26 carbon atoms or a combination thereof covalently linked to the carboxylic acid; and C represents a hydrophilic group covalently linked to the group of B (ii) or (b) A represents a mono-or polyphosphorylated amino acid linked to B by its carboxylic acid to form an amide bond; B represents an amino acid or peptidyl group of 2-10 amino acids, an amino substituted alkyl or alkenyl group comprising 1-26 carbon atoms, an amino substituted polyethylene glycol group comprising 1-26 carbon atoms or a combination thereof covalently linked to A by their amino group; C represents a hydrophilic group covalently linked to the group of B. The invention further relates to a coated metal nanoparticle such as super paramagnetic iron oxide nanoparticle (SPIONs) coated with a plurality of the aforementioned ligands and a method of producing thereof.

A method of preparing a coated nanoparticle can include decomposing a compound to produce a nanoparticle, oxidizing the nanoparticle to produce an oxidized nanoparticle, and coating the oxidized nanoparticle with a zwitterionic ligand to produce the coated nanoparticle. The coated nanoparticle or the nanoparticle can be used in magnetic resonance imaging.

The invention provides a (drug-containing) lipid nanoparticle with: (i) at least one phospholipid; (ii) at least one lysolipid; and (iii) at least one phospholipid comprising a hydrophilic polymer; and (iv) at least one structural lipid of formula (I) which has the following general structure:

##STR00001## wherein R and R are long hydrocarbyl hydrophobic chains, Y is a linker element, and PHG is a polar head group described as large according to its van der Waals radius, and which is different from the phospholipid (i).

The lipid nanoparticle can release a drug (or API) from within the lipid nanoparticle as a result of focused ultrasound (FUS) applied continuously, at least twice, to a desired part of the body to induce hyperthermia (an increase in temperature). FUS is applied after the lipid nanoparticle containing the drug has been administered to the live subject, and causes controlled release of the drug at the desired site of the body. Ultrasound is then halted, and the site of interest allowed to cool. Ultrasound is then applied again. Lipid nanoparticles can be labelled (for MRI, NIRF imaging), enabling real time monitoring of the drug in the human body. Imaging information can be used to direct and guide the nature of the FUS applied to the site of interest.

Provided are a hydrophilic particle, a method for manufacturing the same, and a contrasting agent using the same. More specifically, the hydrophilic particle according to the inventive concept may include a hydrophobic particle, and an amphiphilic organic dye directly absorbed on a surface of the hydrophobic particle. In this case, the hydrophobic particle includes a center particle, and a hydrophobic ligand covering a surface of the center particle, and the amphiphilic organic dye may be combined to the hydrophobic ligand by a hydrophobic interaction. The hydrophilic particle may have a surface zeta potential lower than a surface zeta potential of the amphiphilic organic dye.

The invention relates to non-polymeric lipid-based nanocarrier compositions loaded with metal nanoparticles and at least one therapeutic agent, useful agents for transportation, vectorization, cellular delivery cellular targeting or cellular localization of at least one therapeutic agent.

Methods are provided for the generation of nanostructures suitable for use in magnetic resonance imaging where the nanostructures have at least one dimension of about 2 nm or less. In particular, the methods comprise the selective use of incubation temperatures that result in the controlled removal of ligands from metallic cores to which they are attached, allowing the metallic cores or the precursor moieties to unite to form nanostructures of defined and predictable shapes, but having at least one dimension significantly less that at least one other dimension. Accordingly, the nanostructures of the disclosure may be ultrathin sheets, rods, whiskers and the like, or even structures that are thin and porous resembling rice grains. The temperatures useful in the methods of the disclosure are less than 300 C. and allow for progressive elevation of the incubation temperature. The methods are especially advantageous for synthesizing nanoparticles that may be administered to an animal or human subject for imaging with magnetic resonance. Accordingly, the nanostructures of the disclosure comprise a metallic core, most typically, but not necessarily limited to, a ferrite moiety that can be a ferrous or ferric ion alone or in combination with other metallic elements. However, the methods of the disclosure are also suitable for generating nanostructures with non-ferrous cores such as magnesium or manganese cores.