Conjugated gold nanoparticles
The present invention relates to methods, compositions, and kits for generating conjugated gold nanoparticles. In certain embodiments, the present invention provides methods of generating unsaturated conjugated gold nanoparticles by mixing naked gold nanoparticles with a first type of attachment molecules at a molar ratio such that the attachment molecules attach to the naked gold particles at a density level below the saturation level of the naked gold particles (e.g., at a saturation level of 1-99%). In some embodiments, a second type of attachment molecules (e.g., with the opposite charge as the first type of attachment molecules) are mixed with the unsaturated conjugated gold nanoparticles to generate double-conjugated gold nanoparticles (e.g., that are zwitterionic).
1. A composition comprising: conjugated gold nanoparticles, wherein each of said conjugated gold nanoparticles comprise:
a) a gold nanoparticle comprising a gold surface,
b) a first type of attachment molecules attached to said gold nanoparticle at a density level below the saturation level for said gold nanoparticle, wherein said first type of attachment molecules have the formula R1-polymer-R2,
wherein R1 is a moiety having affinity for said gold surface of said gold nanoparticle, and wherein R2 is a functional group that allows attachment to other chemicals, and/or comprises a targeting ligand, and
c) a second type of attachment molecules attached to said gold nanoparticle, wherein said second type of attachment molecules have the formula R3-polymer-R4, wherein R3 is a moiety having affinity for said gold surface of said gold nanoparticle, and wherein R4 is a functional group that allows attachment to other chemicals, and/or comprises a targeting ligand, and
wherein either: A) said first type of attachment molecules possess a positive charge and said second type of attachment molecules possess a negative charge, or B) said first type of attachment molecules possess a negative charge and said second type of attachment molecules possess a positive charge, and
wherein said conjugated gold nanoparticle posses a ratio of negative to positive attachment molecules of 900/100 to 700/300.
2. The composition of claim 1 , wherein each of said conjugated gold nanoparticles further comprise: a third type of attachment molecules having the formula R5-polymer-R6, wherein R5 is a moiety having affinity for said gold surface of said gold nanoparticle, and wherein R6 is a functional group that allows attachment to other chemicals, and/or comprises a targeting ligand.
3. The composition of claim 1 , wherein said R1 is the same or different on each of said first type of attachment molecules and is selected from the group consisting of: a thiol group, an amine group, a phosphine group, and a disulfide group.
4. The composition of claim 1 , wherein said R3 is the same or different on each of said second type of attachment molecules and is selected from the group consisting of: a thiol group, an amine group, a phosphine group, and a disulfide group.
5. The composition of claim 1 , wherein said polymer in said first type of attachment molecules comprises polyethylene glycol.
6. The composition of claim 1 , wherein said polymer in said first type of attachment molecules is selected from the group consisting of: polyethyleneglycol (PEG), polyacrylamide, polydecylmethacrylate, polystyrene, dendrimer molecule, polycaprolactone (PCL), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), polyglycolic acid (PGA), polyhydroxybutyrate (PHB), and the said polymer has degree of polymerization in the range from 1 unit to 100 units.
7. The composition of claim 1 , wherein said polymer in said second type of attachment molecules comprises polyethylene glycol.
8. The composition of claim 1 , wherein said polymer in said second type of attachment molecules is selected from the group consisting of: polyethyleneglycol (PEG), polyacrylamide, polydecylmethacrylate, polystyrene, dendrimer molecule, polycaprolactone (PCL), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), polyglycolic acid (PGA), polyhydroxybutyrate (PHB), and the said polymer has degree of polymerization in the range from 1 unit to 100 units.
9. The composition of claim 1 , wherein said R2 is selected from the group consisting of COOH, —OCH3, and —NH2.
10. The composition of claim 1 , wherein said R4 is selected from the group consisting of COOH, —OCH3, and —NH2.