Photothermal nanostructures in tumor therapy

Abstract

Methods, structures, devices and systems are disclosed for implementing a photothermal therapy using nanostructures. In one aspect, a device to produce a photothermal effect includes a particle having a molecular layer functionalized onto the external surface of the particle and structured to attach to one or more targeting molecules capable of binding to a receptor site of a cell, in which the particle is configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the particle to emit heat energy. In some implementations, the device is deployed in an organism having a tumor that includes a plurality of the cell and binds to the receptor site of the tumor by the targeting molecules, in which the light energy is emitted at a region of the organism that contains the tumor and the heat energy causes cellular death of the tumor cell.

1 . A device for producing a photothermal effect, comprising:
 a particle having a molecular layer functionalized onto the external surface of the particle and structured to attach to one or more targeting molecules capable of binding to a receptor site of a cell, wherein the particle is configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the particle to emit heat energy.   
     
     
         2 . The device of  claim 1 , wherein the one or more targeting molecules include tumor-targeting antibodies including an anti-epidermal growth factor receptor antibody. 
     
     
         3 . The device of  claim 2 , wherein the device is deployed in an organism having a tumor that includes a plurality of the cell and binds to the receptor site of the tumor by the targeting molecules, wherein the light energy is emitted at a region of the organism that contains the tumor, and wherein the heat energy causes cellular death of the tumor cell. 
     
     
         4 . The device of  claim 1 , wherein the particle has a length dimensions in a nanometer range. 
     
     
         5 . The device of  claim 1 , wherein the particle is configured from a material that includes at least one of gold, silver, iron, carbon, or silicon. 
     
     
         6 . The device of  claim 1 , wherein the particle is configured as at least one of a rod, sphere, cone, cage, cube, or tube. 
     
     
         7 . The device of  claim 1 , wherein the particle includes an aspect ratio of 4:1. 
     
     
         8 . The device of  claim 1 , wherein the particular wavelength is in a near infrared range. 
     
     
         9 . The device of  claim 1 , wherein the molecular layer includes polyethylene glycol. 
     
     
         10 . The device of  claim 1 , wherein the one or more targeting molecules are structured to attach a fluorophore. 
     
     
         11 . A method for producing photothermal nanorods, comprising:
 fabricating nanorod structures, the nanorod structures configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the particle to emit heat energy;   coating the nanorod structures with a biocompatible molecular layer, and   conjugating the biocompatible molecular layer-coated nanorod structures with a targeting ligand and an imaging agent to form functionalized photothermal nanorods, the conjugating including:
 determining a molar ratio of a cross-linking agent to the targeting ligand, 
 adding the targeting ligand at a particular amount to a linker solution containing the cross-linking agent to form a ligand cross-linker solution, the linker solution having a particular concentration of the cross-linking agent to comply with the determined molar ratio, 
 adding the imaging agent at a particular amount to the ligand cross-linker solution to form an imager ligand cross-linker solution, and 
 reacting the biocompatible molecular layer-coated nanorod structures with the imager ligand cross-linker solution. 
   
     
     
         12 . The method of  claim 11 , wherein the biocompatible molecular layer includes polyethylene glycol. 
     
     
         13 . The method of  claim 11 , wherein the cross-linking agent includes long chain succinimidyl 6-(3-[2-pyridyldithio]-propionamido) hexanoate (LC-SPDP) and the linker solution includes dimethyl sulfoxide (DMSO), wherein the particular concentration of the LC-SPDP in the linker solution is 20 mM. 
     
     
         14 . The method of  claim 11 , wherein the adding the targeting ligand to the linker solution includes incubating for about 1 hour at room temperature. 
     
     
         15 . The method of  claim 11 , wherein the molar ratio of the cross-linking agent to the targeting ligand is 300:1 or within fifty percent of 300:1. 
     
     
         16 . The method of  claim 11 , wherein the particular amount of the imaging agent added to the ligand cross-linker solution is in a range from 2 μL to 20 IA. 
     
     
         17 . The method of  claim 11 , wherein the reacting includes incubating at room temperature for at least eight hours. 
     
     
         18 . The method of  claim 11 , further comprising removing reaction byproducts formed during the conjugating. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . A photothermal nano structure device, comprising:
 a structure structured in the form of a rod, sphere, cone, cage, cube, or tube having at least one dimension within a nanometer scale, the structure configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the particle to emit heat energy;   a biocompatible molecular layer formed on at least part of the exterior of the structure, and   a molecular probe attached to the biocompatible molecular layer, the molecular probe including a targeting ligand conjugated to an imaging agent, the targeting ligand capable of binding to a receptor site of a cell,   wherein the molecular probe is formed by determining a molar ratio of a cross-linking agent to the targeting ligand, adding the targeting ligand at a particular amount to a linker solution containing the cross-linking agent to form a ligand cross-linker solution, the linker solution having a particular concentration of the cross-linking agent to comply with the determined molar ratio, and adding the imaging agent at a particular amount to the ligand cross-linker solution to form an molecular probe in solution.   
     
     
         25 . The device of  claim 24 , wherein the targeting ligand is a tumor-targeting antibody. 
     
     
         26 . The device of  claim 25 , wherein the tumor-targeting antibody includes anti-epidermal growth factor receptor antibody. 
     
     
         27 . The device of  claim 24 , wherein the device is deployed in an organism having a tumor that includes a plurality of the cell and binds to the receptor site of the tumor by the targeting ligand, wherein the light energy is emitted at a region of the organism that contains the tumor, and wherein the heat energy causes cellular death of the tumor cell. 
     
     
         28 . The device of  claim 27 , wherein the device is deployed in the organism by direct injection into the tumor. 
     
     
         29 . The device of  claim 24 , wherein the structure is configured from a material that includes at least one of gold, silver, iron, carbon, or silicon. 
     
     
         30 . The device of  claim 24 , wherein the structure includes an aspect ratio of 4:1. 
     
     
         31 . The device of  claim 24 , wherein the particular wavelength is in a near infrared range. 
     
     
         32 . The device of  claim 24 , wherein the biocompatible molecular layer includes polyethylene glycol. 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . A method to administer a photothermal therapy by direct injection of nanoparticles into a tissue, comprising:
 injecting a photothermal nanoparticle device directly into a tumor in an organism, the photothermal nanoparticle device comprising a nanostructure having a molecular layer functionalized onto an external surface of the nano structure, the nanostructure configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the nanostructure to emit heat energy; and   emitting the light energy at a region of the organism that contains the tumor,   wherein the heat energy causes cellular death of cells of the tumor.   
     
     
         38 . The method of  claim 37 , wherein the molecular layer is functionalized to the nanostructure at a concentration in a range of 1.12-4.41 mg/mL or in an optical density range of 2.06-8.24. 
     
     
         39 . A method to administer a photothermal therapy by direct injection of nanoparticles into a tissue, comprising:
 injecting a photothermal nanoparticle device directly into a tumor in an organism, the nano structure configured to absorb light energy at a particular wavelength to produce a plasmon resonance effect that causes the nano structure to emit heat energy; and   emitting the light energy at a region of the organism that contains the tumor,   
       wherein the heat energy causes cellular death of cells of the tumor.