Metal oxide nanoparticle for cell lysis

Abstract

A nanostructure comprises a MOX NP and a bidentate ligand on a surface of the MOX NP. A cancer recognition molecule is covalent coupled to the surface of the MOX NP via the bidentate ligand. A biocatalyst is also coupled to the surface of the MOX nanoparticle via the bidentate ligand. The cancer recognition molecule includes a structure configured to selectively recognize a corresponding antigen on a surface of a cancer cell and bind to the antigen. The biocatalyst is structured to selectively catalyze the oxidation of a light emitting compound to produce photons. The photons transform the MOX NPs into an excited state such that the MOX NPs generate reactive oxygen species (ROS) in the vicinity of the cancer cells in the excited state. The reactive oxygen species lyse or cause apoptosis in the cancer cells in situ. The biocatalyst includes luciferase and the light emitting compound includes luciferin.

What is claimed is: 
     
         1 . A nanostructure, comprising:
 a metal oxide (MOX) nanoparticle;   a bidentate ligand disposed on a surface of the MOX nanoparticle;   a cancer recognition molecule covalently coupled to the surface of the MOX nanoparticle via the bidentate ligand; and   a biocatalyst coupled to the surface of the MOX nanoparticle via the bidentate ligand,   wherein, the cancer recognition molecule comprises a structure configured to selectively recognize a corresponding antigen on a surface of a cancer cell and bind to the antigen, and wherein the biocatalyst is structured to selectively catalyze the oxidation of a light emitting compound to produce photons, the photons transforming the MOX nanoparticles into an excited state, the MOX nanoparticles generating reactive oxygen species in the vicinity of the cancer cells in the excited state, the reactive oxygen species configured to at least one of lyse the cancer cell or cause apoptosis in the cancer cell.   
     
     
         2 . The nanostructure of  claim 1 , wherein the MOX nanoparticles include at least one of TiO 2 , Fe x O y , CeO 2 , ZrO 2 , V x O y , Mo x O y , Mn x O y , NiO, AgO and Cu x O y  nanoparticles. 
     
     
         3 . The nanostructure of  claim 2 , wherein the MOX nanoparticles include a hybrid metal/MOX nanoparticle. 
     
     
         4 . The nanostructure of  claim 3 , wherein the metal included in the hybrid metal/MOX nanoparticle includes at least one of Au and Ag. 
     
     
         5 . The nanostructure of  claim 3 , wherein the hybrid metal/MOX nanoparticles include at least one of a core-shell and dumbbell shaped nanoparticles 
     
     
         6 . The nanostructure of  claim 2 , wherein the MOX nanoparticles include TiO 2  nanoparticles. 
     
     
         7 . The nanostructure of  claim 1 , wherein the bidentate ligand includes 3,4-dihydroxyphenylacetic acid (DOPAC). 
     
     
         8 . The nanostructure of  claim 1 , wherein the biocatalyst includes luciferase, and wherein the light emitting compound includes luciferin, and wherein the luciferase catalyzes the oxidation of luciferin in the presence of adenosine triphosphate (ATP). 
     
     
         9 . The nanostructure of  claim 1 , wherein the cancer recognition molecule comprises C225 antibody or IL13. 
     
     
         10 . A method of treating cancer using a nanostructure comprising a MOX nanoparticle having a cancer recognition molecule and a biocatalyst coupled to a surface of the MOX nanoparticle via a bidentate ligand, the method comprising:
 injecting a plurality of nanostructures into a blood stream of a patient having cancer cells, the cancer cells producing adenosine triphosphate (ATP);   incubating the nanostructures within the blood stream of the patient for a first predetermined time;   selectively binding the plurality of nanoparticles to the cancer cells via the cancer recognition molecule;   injecting a light emitting compound into the blood stream of the patient;   incubating the light emitting compound in the blood stream of the patient for a second predetermined time, the incubating allowing the light emitting compound to be transported to the nanostructures selectively bound on the cancer cells;   oxidizing the light emitting compound catalyzed by the biocatalyst in the presence of the ATP to produce photons in proximity of the cancer cells;   exciting the MOX nanoparticles via the photons to generate reactive oxygen species in proximity of the cancer cells; and   at least one of lysing or causing apoptosis in the cancer cells in situ by interaction with the reactive oxygen species.   
     
     
         11 . The method of  claim 10 , wherein the MOX nanoparticles include TiO 2 . 
     
     
         12 . The method of  claim 10 , wherein the bidentate ligand includes DOPAC. 
     
     
         13 . The method in  claim 10 , wherein the cancer recognition molecule is monoclonal antibody C225 or IL13. 
     
     
         14 . The method of  claim 11 , wherein the biocatalyst includes luciferase, and wherein the light emitting compound includes luciferin. 
     
     
         15 . The method of  claim 11 , wherein the cancer cells include at least one of colorectal cancer cells, pancreatic cancer cells, liver cancer cells, prostate cancer cells, stomach cancer cells, throat cancer cells, brain cancer cells, melanoma, A172 human glioblastoma, astrocytoma, IL-13Ra2-positive U251 MG cells and IL-13Ra2-positive cancer cells. 
     
     
         16 . The method of  claim 10 , further comprising:
 exposing the MOX nanoparticle to a magnetic field, the magnetic field enhancing the generation of the reactive oxygen species and increasing an efficiency of the lysing of the cancer cells.   
     
     
         17 . A method of formulating a cancer treating composition, comprising:
 incubating a biocatalyst with a bidentate linker in a buffer solution at a predetermined pH, the incubating causing the biocatalyst to covalently couple to the bidentate linker, thereby forming a biocatalyst coupled bidentate linker;   incubating the biocatalyst coupled bidentate linker with metal oxide (MOX) nanoparticles so as to covalently couple the MOX nanoparticles to the bidentate linker and, thereby the biocatalyst; and   separately, incubating a cancer recognition molecule with the bidentate linker so as to covalently couple the cancer recognition molecule to the bidentate linker, thereby forming a cancer recognition molecule coupled bidentate linker; and   incubating the cancer recognition molecule coupled bidentate linker with the MOX nanoparticles coupled to the biocatalyst, the incubating causing the cancer recognition molecule to be also coupled to the MOX nanoparticles via the bidentate linker so as to form the cancer treating composition,   wherein, the cancer recognition molecule comprises a structure configured to selectively recognize a corresponding antigen on a surface of a cancer cell and bind to the antigen, and wherein the biocatalyst is structured to selectively catalyze the oxidation of a light emitting compound to produce photons, the photons transforming the MOX nanoparticles into an excited state, the MOX nanoparticles configured to generate reactive oxygen species in the vicinity of the cancer cells in the excited state, the reactive oxygen species lysing or causing apoptosis in the cancer cell.   
     
     
         18 . The method of formulating a cancer treating composition of  claim 17 , wherein the MOX nanoparticles include at least one of TiO 2 , Fe x O y , CeO 2 , ZrO 2 , V x O y , Mo x O y , Mn x O y , NiO, AgO and Cu x O y  nanoparticles. 
     
     
         19 . The method of formulating a cancer treating composition of  claim 17 , wherein the bidentate ligand include 3,4-dihydroxyphenylacetic acid (DOPAC), and wherein each of the biocatalyst, the MOX nanoparticles and the cancer recognition molecule are covalently coupled to the DOPAC using a carbodiimide linking chemistry. 
     
     
         20 . The method of formulating a cancer treating composition of  claim 17 , wherein the biocatalyst includes luciferase, and wherein the light emitting compound includes luciferin, and wherein the luciferase catalyzes the oxidation of luciferin in the presence of adenosine triphosphate (ATP).