Metal-encapsulated carbonaceous dots
View Patent ↗Nanoparticles described as metal-encapsulated carbonaceous dots or M@C-dots are disclosed. Also disclosed are specific M@C-dots with gadolinium, so called Gd@C-dots. These nanoparticles are biologically inert and preclude the release of metal in biological environments. In addition, despite a dimension exceeding the commonly recognized threshold for renal clearance, the disclosed nanoparticles can be efficiently cleared via urine after systematic injection. Methods of making and using such nanoparticles are also disclosed.
1. A nanoparticle, comprising: gadolinium encapsulated in an amorphous carbon shell, wherein the shell comprises carboxyl groups and wherein the average diameter of the nanoparticle is from about 2 nm to about 34 nm.
2. The nanoparticle of claim 1 , wherein the gadolinium is Gd(III).
3. The nanoparticle of claim 1 , wherein the average diameter is from about 10 nm to about 14 nm.
4. The nanoparticle of claim 1 , wherein the average diameter is about 12 nm.
5. The nanoparticle of claim 1 , wherein the nanoparticle has a r 1 relaxivity of from about 0 to about 50 mM −1 s −1 .
6. The nanoparticle of claim 1 , wherein the nanoparticle has a r 1 relaxivity of from about 5 to about 25 mM −1 s −1 .
7. The nanoparticle of claim 1 , wherein the nanoparticle has a quantum yield of from about 0 to about 80%.
8. The nanoparticle of claim 1 , wherein the nanoparticle has a quantum yield of from about 15 to about 50%.
9. The nanoparticle of claim 1 , wherein the nanoparticle is conjugated to a targeting moiety.
10. The nanoparticle of claim 1 , wherein the nanoparticle is conjugated to a cyclic RDG peptide.
11. The nanoparticle of claim 1 , wherein the nanoparticle is conjugated to Herceptin, Avastin, Erbitux, doxorubicin, methotrexate or paclitaxel, or polyethylenimine.
12. A method of imaging cancer in a subject, comprising:
administering to the subject the nanoparticle of claim 1 ; and detecting a fluorescent and/or magnetic resonance signal from the cancer.
13. A method of making the nanoparticle of claim 1 , comprising:
calcining gadolinium with a chelator.
14. The method of claim 13 , wherein the chelator is diethylenetriaminepentacetate.
15. The method of claim 13 , wherein the chelator is 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7,10-tetraazacyclodode-cane-1, 4, 7,10-tetraacetic acid (DOTA), 1,4,8,11-tetraazacyclododenane-1,4,8,11-tetraacetic acid (TETA), 2,2′-(1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diyl)diacetic acid (CB-TE2A), 3,6,9,15-Tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA), pendetide (GYK-DTPA), cyclohexyldiethylenetriaminepentaacetic acid (CHX-DTPA), 2-(4,7-biscarboxymethyl[1,4,7]triazacyclonona-1-yl-ethyl)carbonyl-methylamino]acetic acid (NETA), diethylene triamine pentaacetic acid (DTPA), desferrioxamine, nitrilotriacetate (NTA), DO3A, ethylenediammine, acetylacetonate, phenanthroline, oxalate, citric acid, bipyridine, cyanide, nitrite, acetonitrile, ethylenediamine tetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), poly-1-lysine, polyethylenimine, or polyvinylpyrrolidone (PVP), or any salt, derivative, functionalized analog, or mixture of these.
16. A nanoparticle, comprising: a metal encapsulated in an amorphous carbon shell, wherein the shell comprises carboxyl groups and wherein the average diameter of the nanoparticle is from about 2 nm to about 34 nm.
17. The nanoparticle of claim 16 , wherein the metal is Fe, Mn, Ti, Co, Ni, Cu, Zn, Ga, Ge, Y, Au, Ag, Pt, Cr, Cd, Pb, Ce, Eu, Dy, Tb, Ho, Er, Tm, or Yb.
18. A method of making the nanoparticle of claim 16 , comprising:
calcining a metal with a chelator.
19. The method of claim 18 , wherein the metal is Fe, Mn, Ti, Co, Ni, Cu, Zn, Ga, Ge, Y, Au, Ag, Pt, Cr, Cd, Pb, Ce, Eu, Dy, Tb, Ho, Er, Tm, or Yb.
20. The method of claim 18 , wherein the chelator is diethylenetriaminepentacetate, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7,10-tetraazacyclodode-cane-1, 4, 7,10-tetraacetic acid (DOTA), 1,4,8,11-tetraazacyclododenane-1,4,8,11-tetraacetic acid (TETA), 2,2′-(1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diyl)diacetic acid (CB-TE2A), 3,6,9,15-Tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA), pendetide (GYK-DTPA), cyclohexyldiethylenetriaminepentaacetic acid (CHX-DTPA), 2-(4,7-biscarboxymethyl[1,4,7]triazacyclonona-1-yl-ethyl)carbonyl-methylamino]acetic acid (NETA), diethylene triamine pentaacetic acid (DTPA), desferrioxamine, nitrilotriacetate (NTA), DO3A, ethylenediammine, acetylacetonate, phenanthroline, oxalate, citric acid, bipyridine, cyanide, nitrite, acetonitrile, ethylenediamine tetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), poly-1-lysine, polyethylenimine, or polyvinylpyrrolidone (PVP) or any salt, derivative, functionalized analog, or mixture of these.