Nanoparticle-loaded cells

Abstract

The invention provides nanoparticle-loaded cells and compositions useful for improved imaging and therapy, for example radio-therapy. The invention also provides methods of manufacture of nanoparticle-loaded cells, methods of administering the nanoparticle-loaded cells, and methods for treatment and/or imaging.

1 . A cell comprising one or more nanoparticles wherein the cell is a mesenchymal stem cell (MSC) and the one or more nanoparticles comprises a high-Z element, wherein the high-Z element has an atomic number of at least 27 and wherein the high-Z element is in a majority amount in the one or more particles by weight. 
     
     
         2 . A cell comprising one or more nanoparticles wherein the cell is a mesenchymal stem cell (MSC) and the one or more nanoparticles comprises a high-Z element, wherein the high-Z element has an atomic number of at least 27 and wherein the high-Z element is in a primary image enhancer. 
     
     
         3 . A cell comprising one or more nanoparticles wherein the cell is a mesenchymal stem cell (MSC), wherein the nanoparticle comprises a core and the core comprises a high-Z material selected from the group consisting of high-Z elements with an atomic number of at least 27, heavy metal oxides, superconductors, paramagnetic materials, and quantum dots. 
     
     
         4 . The cell of  claim 3  wherein the high-Z material comprises gold or iron-oxide. 
     
     
         5 . The cell of  claim 4  wherein the majority of the one or more nanoparticles has a diameter in a range of about 0.1 nm to about 20 nm. 
     
     
         6 . The cell of  claim 5  wherein the total mass of the one or more nanoparticles is in a range of about 0.05 atto grams to about 500 atto grams. 
     
     
         7 . The cell of  claim 5  wherein the one or more nanoparticles is present in a range of about 1 to about 10,000 nanoparticles. 
     
     
         8 . The cell of  claim 7  wherein the total mass of the one or more nanoparticles is in a range of about 0.05 atto grams to about 500 atto grams. 
     
     
         9 . The cell of  claim 5  wherein the high-Z element is gold. 
     
     
         10 . A composition comprising a plurality of MSC cells wherein at least about 1% of the MSC cells comprise one or more nanoparticles, wherein the nanoparticle comprises a gold or iron-oxide core, and wherein the majority of the one or more nanoparticles has a diameter in a range of about 0.1 nm to about 20 nm. 
     
     
         11 . The composition of  claim 10  wherein the plurality of MSC cells are present in an amount of at least about 100,000 in number. 
     
     
         12 . The composition of  claim 11  wherein at least about 10% of the MSCs comprise one or more nanoparticles, wherein the nanoparticle comprises a gold or iron-oxide core, and wherein the majority of the one or more nanoparticles has a diameter in a range of about 0.1 nm to about 20 nm. 
     
     
         13 . The composition of  claim 11  wherein the high-Z element is gold. 
     
     
         14 . The composition of  claim 11  wherein at least about 70% of the cells are viable after a cryoprotective freeze-thaw cycle. 
     
     
         15 . The composition of  claim 14  wherein at least about 10% of the MSCs comprise one or more nanoparticles, wherein the nanoparticle comprises a gold or iron-oxide core, and wherein the majority of the one or more nanoparticles has a diameter in a range of about 0.1 nm to about 20 nm. 
     
     
         16 . The composition of  claim 14  wherein the nanoparticles are in an amount of at least 5 femtograms. 
     
     
         17 . The composition of  claim 16  in a therapeutically effective amount and wherein the high-Z element is gold. 
     
     
         18 . The composition of  claim 14  wherein the high-Z element is gold and wherein upon administration to a subject with a tumor or cancer followed by irradiation of the diseased tissue with therapeutic radiation, an increased therapeutic efficacy is attained compared to irradiation alone. 
     
     
         19 . A method of treating a diseased tissue in a subject comprising a step of administering the composition of  claim 11  to the subject and a subsequent step of irradiating the diseased tissue with therapeutic radiation, optionally wherein the diseased tissue releases MSC chemo-attractants. 
     
     
         20 . A method of detecting a diseased tissue in a subject comprising a step of administering the composition of  claim 11  to the subject and a subsequent step of imaging the subject or a portion thereof and detecting the nanoparticles.