Compounds and compositions for treating leishmaniasis and methods of diagnosis and treating using same
Compositions and methods of using these compositions that can include a targeting moiety and a therapeutic agent are described herein. These compositions can be used for treating inflammatory diseases, such as parasitic diseases that result in cutaneous lesions. For example, and without limitation, such an parasitic disease can be leishmaniasis.
1. A method of treating leishmaniasis comprising administering to a subject in need thereof an effective amount of a compound comprising a dextran backbone having one or more CD206 targeting moieties and one or more therapeutic agents attached thereto; wherein the compound is effective for treatment of leishmaniasis disease; and wherein the compound is 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 and wherein at least one L 1 and at least one L 2 comprises a biodegradable linker;
each A independently comprises a therapeutic agent or a detection label or H; each R independently comprises a CD206 targeting moiety or H; and
n is an integer greater than zero; and
wherein at least one R is a CD206 targeting moiety selected from the group consisting of mannose, fucose, and n-acetylglucosamine and at least one A is a therapeutic agent; and
wherein the compound comprises at least one L 1 -A and at least one L 2 -R.
2. A method of targeting tumor-associated macrophages comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 .
3. The method of claim 1 , wherein the compound has at least one therapeutic agent and further comprising at least one detection label.
4. The method of claim 3 , wherein a linker is used to attach the one or more CD206 targeting moieties, one or more therapeutic agents, and the one or more detection labels.
5. The method of claim 1 , wherein the biodegradable linker of the at least one L 1 or the at least one L 2 is an acid-sensitive linker.
6. The method of claim 1 , wherein at least one R is selected from the group consisting of mannose and n-acetylglucosamine.
7. The method of claim 6 , wherein at least one R is mannose.
8. The method of claim 1 , wherein the at least one therapeutic agent is chosen from: amphotericin, isoniazid, heavy metal, paromomycin, miltefosine, fluconazole, pentamide, Meglumine antimoniate, and combinations thereof.
9. The method of claim 1 , wherein the at least one therapeutic agent is doxorubicin or dexamethasone.
10. The method of claim 1 , wherein at least one A is a metal chelator bound to a metal.
11. A method of treating leishmaniasis comprising administering to a subject in need thereof an effective amount of a compound comprising a dextran backbone having one or more CD206 targeting moieties and one or more therapeutic agents attached thereto; wherein the compound is effective for treatment of leishmaniasis disease; and wherein the compound is 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, and
wherein at least one L 1 and at least one L 2 comprises a biodegradable linker;
each A independently comprises a therapeutic agent or a detection label or H; each R independently comprises a CD206 targeting moiety or H; and
n is an integer greater than zero;
wherein the CD206 targeting moiety is mannose, and the therapeutic agent comprises doxorubicin or dexamethasone; and
wherein the compound comprises at least one L 1 -A and at least one L 2 -R.