Laser activated nanothermolysis of cells

Abstract

Provided herein are methods and systems to increase selective thermomechanical damage to a biological body, such as a cancer cell or cell associated with a pathophysiological condition. The biological body or cancer cell is specifically targeted with nanoparticulates comprising one or more targeting moieties which form nanoparticulate clusters thereon or therewithin. Pulsed electromagnetic radiation, e.g., optical radiation, having a wavelength spectrum selected for a peak wavelength near to or matching a peak absorption wavelength of the nanoparticulates selectively heats the nanoparticulates thereby generating vapor microbubbles around the clusters causing damage to the targets without affecting any surrounding medium or normal cells or tissues. Also provided are methods for treating leukemia and for selectively and thermomechanically causing damage to cells associated with a pathophysiological condition using the methods and system described herein.

What is claimed is: 
     
         1 . A method for increasing selective therapeutic thermomechanically induced damage to a biological body, comprising:
 specifically targeting a biological body comprising a medium with a plurality of nanoparticulates each conjugated to at least one targeting moiety, said nanoparticulates effective to form one or more nanoparticulate clusters on or in the biological body upon targeting thereto;   irradiating the biological body with at least one pulse of electromagnetic radiation having a spectrum of wavelengths selected to have a peak wavelength that is near to or that matches a peak absorption wavelength of the nanoparticulates; and   generating vapor microbubbles from heat produced via absorption of the electromagnetic radiation into the nanoparticulate cluster(s), wherein the vapor microbubbles cause selective and increased thermomechanical damage to the targeted biological body.   
     
     
         2 . The method of  claim 1 , further comprising:
 filtering the products of the thermomechanical damage from the medium.   
     
     
         3 . The method of  claim 1 , further comprising:
 receiving a photothermal signal or generating an optical image of thermomechanical effects to monitor and to guide selective thermomechanical damage to the biological body.   
     
     
         4 . The method of  claim 1 , wherein the nanoparticulate has a dimension of about 1 nm to about 1000 nm. 
     
     
         5 . The method of  claim 1 , wherein the nanoparticulate cluster has a total volume about 2 to about 200 times greater than a volume of the nanoparticulate comprising the same. 
     
     
         6 . The method of  claim 1 , wherein the nanoparticulate is a spherical nanoparticle, a nanorod or a nanoshell at least partially comprising gold or silver or is a carbon nanotube. 
     
     
         7 . The method of  claim 1 , wherein the targeting moiety is a monoclonal antibody or a peptide specifically targeted to a receptor site on the biological body. 
     
     
         8 . The method of  claim 7 , wherein the receptor site further comprises another monoclonal antibody or peptide attached thereto specific for the targeted monoclonal antibody. 
     
     
         9 . The method of  claim 7 , wherein the nanoparticulate further comprises complementary strands of a nucleic acid conjugated thereto or a combination thereof. 
     
     
         10 . The method of  claim 7 , wherein the nanoparticulate further comprises PEG molecules. 
     
     
         11 . The method of  claim 1 , wherein the wavelength spectrum is a range of wavelengths of about 300 nm to about 300 mm. 
     
     
         12 . The method of  claim 1 , wherein the pulse of electromagnetic radiation is optical radiation. 
     
     
         13 . The method of  claim 12 , wherein the pulse of optical radiation has wavelength in the range from 500 nm to 1150 nm. 
     
     
         14 . The methods of  claim 1 , wherein the pulse of electromagnetic radiation is about 1 ns to about 100 ns in duration. 
     
     
         15 . The method of  claim 1 , wherein the biological body is an abnormal cell, a bacterium or a virus. 
     
     
         16 . A system for increasing selective therapeutic thermomechanical damage to abnormal cells, comprising:
 a chamber containing the abnormal cells in a medium;   a source of nanoparticulates modified to specifically target the abnormal cells fluidly connected to the cell chamber;   an optical chamber adapted to contain the targeted abnormal cells fluidly connected to the cell chamber;   a pulsed source of electromagnetic radiation directed against the targeted cancer cells in the optical chamber, said source configured to emit a spectrum of wavelengths selected to have a peak wavelength that is near to or that matches a peak absorption wavelength of said nanoparticulates; and   means for filtering out cells damaged by thermomechanical effects resulting from absorption of the electromagnetic radiation emitted at the peak wavelength, said filtering means fluidly connected to the cell chamber.   
     
     
         17 . The system of  claim 16 , further comprising:
 means for receiving a photothermal signal or for generating an optical image of the thermomechanical effects.   
     
     
         18 . The system of  claim 16 , wherein the nanoparticulates each comprise at least one targeting moiety specifically targeted to a receptor site on the cancer cell. 
     
     
         19 . The system of  claim 18 , wherein the receptor site further comprises another targeting moiety attached thereto specific for said targeting moiety on the nanoparticulates. 
     
     
         20 . The system of  claim 18 , wherein the targeting moiety is a monoclonal antibody or a peptide attached thereto specific for the targeted monoclonal antibody. 
     
     
         21 . The system of  claim 18 , wherein the nanoparticulate further comprises complementary strands of a nucleic acid conjugated thereto or a combination thereof. 
     
     
         22 . The method of  claim 21 , wherein the nanoparticulate further comprises PEG molecules. 
     
     
         23 . The system of  claim 16 , wherein the nanoparticulate has a dimension of about 1 nm to about 1000 nm. 
     
     
         24 . The system of  claim 16 , wherein the nanoparticulate is a spherical nanoparticle, a nanorod or a nanoshell at least partially comprising gold or silver or is a carbon nanotube. 
     
     
         25 . The system of  claim 16 , wherein the wavelength spectrum is a range of wavelengths of about 300 nm to about 300 mm. 
     
     
         26 . The system of  claim 16 , wherein the pulse of electromagnetic radiation is optical radiation having a wavelength in the range from 500 nm to 1150 nm. 
     
     
         27 . The system of  claim 16 , wherein the pulse of electromagnetic radiation is about 1 ns to about 100 ns in duration. 
     
     
         28 . The system of  claim 16 , wherein the abnormal cells are leukemic cancer cells. 
     
     
         29 . A method for treating a leukemia in an individual, comprising:
 a) obtaining a sample comprising normal and leukemic cells from the individual;   b) placing the sample in the cell chamber of the system of  claim 16 ;   c) targeting the cancer cells in the sample with the modified nanoparticulates, said modified nanoparticulates forming one or more clusters on or in the targeted cancer cell;   d) irradiating the targeted leukemic cells with electromagnetic radiation emitted from the pulsed source, wherein the electromagnetic radiation absorbed by the nanoparticulates causes selective and increased thermomechanical effects damaging to the targeted cancer cells, but not to the normal cells comprising the sample;   e) filtering out the damaged cells from the sample;   f) returning the normal cells remaining in the sample to the individual thereby treating the leukemia; and.   g) repeating said method steps a) to f) zero or more times, thereby treating the leukemia.   
     
     
         30 . The method of  claim 29 , further comprising:
 receiving a photothermal signal or generating an optical image of the thermomechanical effects to monitor and to guide selective thermomechanical damage to the cancer cells.   
     
     
         31 . The method of  claim 29 , wherein the thermomechanical effects are caused by heat generated within the nanoparticulates from absorbed electromagnetic radiation sufficient to form vapor microbubbles around the nanoparticulate clusters. 
     
     
         32 . The method of  claim 29 , wherein the nanoparticulate cluster has a total volume about 2 to about 200 times greater than a volume of the nanoparticulate comprising the same. 
     
     
         33 . A method for selectively and thermomechanically damaging cells associated with a pathophysiological condition, comprising:
 targeting the cells with a first monoclonal antibody specific thereto;   targeting the cells with gold nanoparticulates modified with a second monoclonal antibody specific to the first monoclonal antibody whereupon one or more clusters of the nanoparticulates form on or in the targeted cells;   heating one or more clusters of gold nanoparticulates formed on or in the targeted cells; and   generating vapor bubbles around the heated clusters sufficient to thermomechanically damage the cells.   
     
     
         34 . The method of  claim 33 , further comprising photothermally or optically monitoring the thermomechanical damage. 
     
     
         35 . The method of  claim 33 , wherein the gold nanoparticulates are spherical nanoparticles, nanorods or nanoshells. 
     
     
         36 . The method of  claim 33 , wherein the clustered gold nanoparticulates are heated with optical radiation having a wavelength in a range from 500 nm to 1150 nm. 
     
     
         37 . The method of  claim 33 , wherein the optical radiation is pulsed for a duration of about 1 ns to about 100 ns. 
     
     
         38 . The method of  claim 33 , wherein the nanoparticulate has a dimension of about 1 nm to about 1000 nm. 
     
     
         39 . The method of  claim 33 , wherein the nanoparticulate cluster(s) has a total volume about 2 to about 200 times greater than a volume of the nanoparticulate comprising the same. 
     
     
         40 . The method of  claim 33 , wherein the cell is a cancer cell, a bacterial cell or a virus.