Fluorescent silica-based nanoparticles

Abstract

The present invention provides nanoparticle compositions comprising, for example, a core comprising a fluorescent silane compound; and a silica shell on the core. Also provided are methods for the preparation of nanoparticle compositions including fluorescent nanoparticles, ligated-fluorescent nanoparticles, ligated-fluorescent nanoparticles having therapeutic agents, and ligated-fluorescent nanoparticles coupled or associated with an analyte. Also provided are methods: for the detection of the ligated-fluorescent nanoparticles; for associating the linked-fluorescent nanoparticles with a cellular component of interest and recording or monitoring the movement of the cellular component; for improving the therapeutic properties of the therapeutic agent by combining the therapeutic agent with linked-fluorescent nanoparticles and contacting or administering the combination to a cell or organism; for making and using the fluorescent nanoparticles in, for example, diagnostic agents for the detection of various analytes, and like applications.

What is claimed is:  
     
         1 . A fluorescent nanoparticle comprising: 
 a core comprising a fluorescent silane compound; and    a silica shell on the core.    
     
     
         2 . The nanoparticle of  claim 1  wherein the core comprises the reaction product of a reactive fluorescent compound and an organo-silane, and the shell comprises the reaction product of a silica forming compound.  
     
     
         3 . The nanoparticle of  claim 1  further comprising a ligand on the surface of the fluorescent nanoparticle to form a ligated-fluorescent nanoparticle.  
     
     
         4 . The nanoparticle of  claim 3  wherein the ligand on the surface of the fluorescent nanoparticle is attached by a covalent bond or by physical absorption.  
     
     
         5 . The nanoparticle of  claim 3  wherein the ligand on the surface of the fluorescent nanoparticle is selected from the group consisting of a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, and combinations thereof.  
     
     
         6 . The nanoparticle of  claim 1  wherein the silica shell coating on the core covers from about 10 to about 100 percent of the surface area of the core.  
     
     
         7 . The nanoparticle of  claim 3  wherein the ligand on the surface of the fluorescent nanoparticle covers from about 10 to about 100 percent of the surface area of the core.  
     
     
         8 . The nanoparticle of  claim 1  wherein the thickness of the core to the silica shell is in a ratio of from about 1:1 to about 1:100.  
     
     
         9 . The nanoparticle of  claim 1  wherein the diameter of the nanoparticle is from about 1 to about 1,000 nanometers.  
     
     
         10 . The nanoparticle of  claim 1  further comprising a therapeutic agent.  
     
     
         11 . The nanoparticle of  claim 3  further comprising a therapeutic agent.  
     
     
         12 . The nanoparticle of  claim 10  or  11  wherein the therapeutic agent is selected from the group consisting of a drug, a biomolecule, a surface modifier, and combinations thereof.  
     
     
         13 . The nanoparticle of  claim 10  or  11  wherein the therapeutic agent is absorbed into the silica shell of the nanoparticle.  
     
     
         14 . The nanoparticle of  claim 10  or  11  wherein the therapeutic agent is coated onto the silica shell of the nanoparticle.  
     
     
         15 . The nanoparticle of  claim 3  wherein the therapeutic agent is associated with the ligand of the nanoparticle.  
     
     
         16 . A method of making a fluorescent nanoparticle comprising: 
 mixing a fluorescent compound and an organo-silane compound to form a fluorescent core; and    mixing the resulting core with a silica forming compound to form a silica shell on the core, to provide the fluorescent nanoparticle.    
     
     
         17 . The method of  claim 16  further comprising combining the resulting nanoparticle with a ligand selected from the group consisting of a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, and combinations thereof.  
     
     
         18 . The method of  claim 16  further comprising combining the resulting fluorescent nanoparticle with a therapeutic agent selected from the group consisting of a drug, a biomolecule, a surface modifier, and combinations thereof.  
     
     
         19 . The method of any one of  claim 17  or  18  wherein combining comprises coating the ligand or therapeutic agent onto the surface of the nanoparticle.  
     
     
         20 . The method of any one of  claim 17  or  18  wherein combining comprises imbibing the ligand or therapeutic agent into the surface of the nanoparticle.  
     
     
         21 . The method of any one of  claim 17  or  18  wherein combining comprises bonding the ligand or therapeutic agent to the surface of the resulting nanoparticle.  
     
     
         22 . A method for monitoring movement of a cellular component of a cell comprising: 
 contacting the cell with a ligated-fluorescent nanoparticle to form a cell selectively decorated with the ligated-fluorescent nanoparticle and to form a fluorescent loci; and    recording the motion of the fluorescent loci for a time, to monitor the movement of a cellular component.    
     
     
         23 . The method of  claim 22  wherein the fluorescent loci corresponds to one or more ligated-fluorescent nanoparticle bound to a component of the cell.  
     
     
         24 . The method of  claim 22  wherein the fluorescent loci corresponds to a single ligated-fluorescent nanoparticle bound to a component of the cell.  
     
     
         25 . The method of  claim 22  wherein the ligated-fluorescent nanoparticle is adapted to selectively associate with a cellular component of the cell.  
     
     
         26 . The method of  claim 22  wherein the cellular component is a receptor, an antibody, a hapten, an enzyme, a hormone, a biopolymer, an antigen, a microorganism, a virus, a pathogen, a toxin, and combinations thereof.  
     
     
         27 . The method of  claim 22  wherein the ligated-fluorescent nanoparticle is a fluorescent nanoparticle conjugated with an antibody.  
     
     
         28 . The method of  claim 27  wherein the antibody is an immunoglobin.  
     
     
         29 . The method of  claim 28  wherein the antibody is IgE.  
     
     
         30 . The method of  claim 22  wherein recording is accomplished with a microscopically adapted camera.  
     
     
         31 . The method of  claim 22  wherein recording for a time is from about 1 microsecond to about 30 days  
     
     
         32 . The method of  claim 22  wherein recording for a time is from about 1 second to about 60 minutes.  
     
     
         33 . The method of  claim 22  wherein the contacting and the recording are accomplished in vitro.  
     
     
         34 . The method of  claim 22  wherein the contacting and the recording are accomplished in vivo.  
     
     
         35 . A pharmaceutical carrier comprising the fluorescent nanoparticle of  claim 1 , and optionally a ligand.  
     
     
         36 . A pharmaceutical composition comprising the ligated-fluorescent nanoparticle of  claim 3  and optionally a therapeutic agent.  
     
     
         37 . An imaging agent comprising the ligated-fluorescent nanoparticle of  claim 3 .  
     
     
         38 . A method for treating disease or disorder comprising: 
 administering to a patient in need of treatment an effective amount of a ligated-fluorescent nanoparticle optionally including a therapeutic agent, the nanoparticle being adapted to selectively associate with a disease producing component of the cell, to form a selectively decorated cell with the ligated-fluorescent nanoparticle; and    illuminating the decorated cell to treat disease or disorder.    
     
     
         39 . The method of  claim 38  wherein the ligated-fluorescent nanoparticle fluoresces and heats-up when illuminated.  
     
     
         40 . The method of  claim 38  wherein the ligated-fluorescent nanoparticle is an antibody ligated to a fluorescent nanoparticle.  
     
     
         41 . The method of  claim 38  wherein the disease is cancerous tumor.  
     
     
         42 . The method of  claim 38  wherein the disease in sensitive to fluorescence, heat, or both.  
     
     
         43 . A method of treating a disease or disorder comprising: 
 contacting a cell with a ligated-fluorescent nanoparticle to form a cell selectively decorated with the ligated-fluorescent nanoparticle; and    irradiating the resulting decorated cell for a time to treat the disease or disorder.    
     
     
         44 . A kit for use in the detection of an analyte, the kit comprising packaging material containing a ligated-fluorescent nanoparticle.  
     
     
         45 . A kit for detecting and monitoring a cell surface component, the kit comprising packaging material containing a ligated-fluorescent nanoparticle for detecting the cell surface component, and optionally a recorder for monitoring the cell surface component.  
     
     
         46 . An assay method for detecting motion or a change in the location of a cellular component of a cell when the cell is treated with a therapeutic agent comprising: 
 contacting a cell with a ligated-fluorescent nanoparticle, the nanoparticle having a therapeutic agent, to bind the ligated-fluorescent nanoparticle to a cellular component; and    recording the fluorescent signal, to detect the motion or location change of the component.    
     
     
         47 . The method of  claim 46  further comprising determining the difference between the motion or movement of the bound ligated-fluorescent nanoparticle in the presence and absence of the therapeutic agent.  
     
     
         48 . A method for detecting the presence of an analyte comprising: 
 contacting a sample which may contain an analyte with a ligated-fluorescent nanoparticle adapted to associate with the analyte, if present, to form a ligated-fluorescent nanoparticle-analyte complex;    optionally separating uncomplexed ligated-fluorescent nanoparticle; and    detecting the fluorescent signal of ligated-fluorescent nanoparticle-analyte complex to establish the presence of the analyte.    
     
     
         49 . The method of  claim 48  wherein the ligated-fluorescent nanoparticle-analyte comprises: 
 a ligated-fluorescent nanoparticle where the ligand is selected from the group consisting of a cell component, a biopolymer, a synthetic polymer, an antigen, an antibody, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, and combinations thereof; and  
 an analyte selected from the group consisting of a microorganism, a virus, a cell, a cell component, a biopolymer, a synthetic polymer, an antigen, an antibody, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, and combinations thereof.  
 
     
     
         50 . A fluorescent nanoparticle comprising: 
 a core comprising a fluorescent silane compound; and    a porous silica shell on the core.    
     
     
         51 . The nanoparticle of  claim 50  further comprising a therapeutic agent, a ligand, or mixtures thereof, on the surface of the fluorescent nanoparticle.  
     
     
         52 . The nanoparticle of  claim 51  further comprising a ligand on the surface of the fluorescent nanoparticle.  
     
     
         53 . The nanoparticle of  claim 51  further comprising a therapeutic agent on the surface of the fluorescent nanoparticle.  
     
     
         54 . The nanoparticle of  claim 51  further comprising a magnetic component in the core of the fluorescent nanoparticle.  
     
     
         55 . The method of  claim 16  further comprising treating the fluorescent core with a templating agent prior to forming a silica shell on the core.  
     
     
         56 . The method of  claim 55  wherein the templating agent is a quaternary ammonium salt.  
     
     
         57 . The method of  claim 55  further comprising removing the templating agent after forming a silica shell on the core to afford a porous silica shell.  
     
     
         58 . The method of  claim 57  further comprising treating the porous silica shell with a ligand, a therapeutic, or mixtures thereof.