Compositions for targeting macrophages and other CD206 high expressing cells and methods of treating and diagnosis
Provided are compounds and compositions for targeting macrophages and other CD206 high expressing cells.
1. A compound of Formula (II):
wherein
each X is independently H, L 1 -A, or L 2 -R;
each L 1 and L 2 are independently linkers;
each A independently comprises one selected from the group consisting of a therapeutic agent, a detection label, and H;
each R independently comprises one selected from the group consisting of a CD206 targeting moiety and H;
and
n is an integer greater than zero; and
wherein at least one X is L 1 -A wherein L 1 comprises a hydrazone and at least one X is L 2 -R wherein at least one L 2 comprises —(CH 2 )pS(CH 2 )qNH—, wherein p and q independently are integers from 0 to 5.
2. A compound according to claim 1 , wherein at least one R is selected from mannose, fucose, and n-acetylglucosamine.
3. A compound according to claim 1 , wherein at least one A is selected from a chemotherapeutic agent; an antibiotic; an immunological adjuvant; a compounds useful for treating tuberculosis; a steroid; a nucleotide; a peptide; a protein; microRNA; siRNA; an antiviral; an antigens; or a metal.
4. A compound according to claim 1 , wherein at least one A is a compound useful for treating tuberculosis.
5. A compound according to claim 1 , wherein at least one A is doxorubicin, isoniazid, gadolinium, gallium, silver, or a silver antibiotic.
6. A compound according to claim 1 wherein at least one L 1 is a C 2-12 hydrocarbon chain optionally interrupted by up to three heteroatoms selected from the group consisting of O, S and N.
7. A compound according to claim 1 wherein at least one L 1 comprises (CH 2 ) p S(CH 2 ) q NH, wherein p and q are integers from 0 to 5.
8. A compound according to claim 1 wherein at least one L 2 is a C 2-12 hydrocarbon chain optionally interrupted by up to three heteroatoms selected from the group consisting of O, S and N.
9. A compound according to claim 1 , wherein at least one L 1 -A comprises a chelator.
10. A compound of Formula (4):
wherein
R is mannose,
n is an integer greater than zero, and
11. A compound of Formula (7):
wherein
R is mannose,
R′ is H or CH 3 ,
n is an integer greater than zero, and