Methods compositions and kits for imaging cells and tissues using nanoparticles and spatial frequency heterodyne imaging

Abstract

Methods, compositions, systems, devices and kits are provided herein for preparing and using a nanoparticle composition and spatial frequency heterodyne imaging for visualizing cells or tissues. In various embodiments, the nanoparticle composition includes at least one of: a nanoparticle, a polymer layer, and a binding agent, such that the polymer layer coats the nanoparticle and is for example a polyethylene glycol, a polyelectrolyte, an anionic polymer, or a cationic polymer, and such that the binding agent that specifically binds the cells or the tissue. Methods, compositions, systems, devices and kits are provided for identifying potential therapeutic agents in a model using the nanoparticle composition and spatial frequency heterodyne imaging.

1 - 13 . (canceled) 
     
     
         14 . A method of identifying in a model system a potential therapeutic agent for treating or preventing a disease condition, the method comprising:
 contacting a first sample and a second sample of cells or tissue having the disease condition with a composition including: a nanoparticle and at least one of a polymer layer coating the nanoparticle and a binding agent that specifically binds the disease agent;   contacting the second sample with the potential therapeutic agent; and,   measuring a presence or an amount of a marker in the first sample and the second sample, wherein the marker is characteristic of the disease condition, wherein a greater amount of the marker in the first sample compared to that in the second sample is a measure of treatment and protection by the potential therapeutic agent, thereby identifying the potential therapeutic agent for treating or preventing the disease condition.   
     
     
         15 . The method according to  claim 14 , wherein detecting the presence of the marker in the first sample and the second sample comprises measuring or detecting the nanoparticle using X-ray scatter imaging or spatial frequency heterodyne imaging. 
     
     
         16 . The method according to  claim 14 , wherein prior to contacting, the method further comprises constructing the nanoparticle or a plurality of nanoparticles comprising at least one material selected from the group of: a metal, a metal oxide, a magnetic resonance imaging agent, and a combination thereof. 
     
     
         17 . The method according to  claim 16 , wherein constructing the nanoparticle comprises forming a shell or core of the nanoparticle with at least one from the group of: with at least one of: silver, copper, gold, cadmium, zinc, nickel, palladium, platinum, rhodium, platinum, manganese, gadolinium, dysprosium, tantalum, titanium, and iron. 
     
     
         18 . The method according to  claim 14 , wherein the binding agent comprises at least one selected from the group of: a drug, a protein, a carbohydrate, and a nucleotide sequence. 
     
     
         19 . The method according to  claim 14 , wherein the disease condition is associated with or produced by at least one from the group of: a virus, a tumor, a cancer, a fungus, a bacterium, a parasite, a pathogenic molecule, and a protein. 
     
     
         20 . The method according to  claim 14 , wherein prior to contacting, the method further comprises constructing the nanoparticle by attaching or conjugating the binding agent to an external surface of the nanoparticle, wherein the binding agent comprises at least one selected from the group of: a drug, a protein, a carbohydrate, and a nucleotide sequence. 
     
     
         21 . The method according to  claim 20 , wherein the protein is an antibody selected from the group of: a monoclonal antibody; a polyclonal antibody; a single-chain antibody (scFv); a recombinant heavy-chain-only antibody (VHH); an Fv; a Fab; a Fab′; and a F(ab′) 2 . 
     
     
         22 . The method according to  claim 14 , wherein measuring further comprises observing a localization of the marker in the cells or the tissue of the first sample and the second sample. 
     
     
         23 . The method according to  claim 14 , further comprising spatial frequency heterodyne imaging the nanoparticles in the cells or the tissue using an absorption grid and a detector. 
     
     
         24 . A kit for imaging cells or a tissue in a subject comprising:
 a composition comprising a nanoparticle including at least one selected from the group of: a polymer layer and a binding agent, wherein the composition binds to and/or is phagocytosed by the cells or the tissue;   instructions for use, wherein the instructions describe: contacting the cells or the tissue with the composition, and imaging the cells and the tissue and detecting X-ray scattering of the composition with a device;   and a container.   
     
     
         25 . The kit according to  claim 24 , wherein the nanoparticles comprise at least one selected from the group of: a metal, a metal oxide, an inorganic material, an organic material, a magnetic resonance imaging agent, and a combination thereof. 
     
     
         26 . A composition for imaging cells or a tissue comprising:
 a metal nanoparticle having attached to an external surface of the nanoparticle a polymer layer, and FB50 monoclonal antibody that specifically binds an antigen of hepatocellular carcinoma, wherein the polymer layer comprises at least one of: a polyethylene glycol, a polyelectrolyte, an anionic polymer, and a cationic polymer.