Abstract: Provided are methods of attaching a mannose-binding C-type lectin receptor targeting moiety to a polymeric carbohydrate backbone using an amide linkage. The amide linkage may be found between a leash, such as an amine terminated leash, and the mannose-binding C-type lectin receptor targeting moieties. The compounds and compositions disclosed utilizing the amide linkage provide for highly stable compounds with a significant reduction in loss of mannose-binding C-type lectin receptor targeting moieties from the polymeric carbohydrate backbone.

Abstract: Provided are compounds, compositions, methods, and kits for increasing target specificity of a mannosylated carbohydrate polymeric therapeutic or diagnostic compound to reduce or eliminate localization of the mannosylated carbohydrate polymeric therapeutic or diagnostic compound to off-target sites. Mannosylated carbohydrate polymers are synthesized to be modified to be either polyanionic (i.e., net negatively charged) or electrostatically neutral, and using these polyanionic or neutral mannosylated carbohydrate polymers as competitors for polycationic (i.e., net positively charged) mannosylated carbohydrate polymers carrying small molecule drug payloads or imaging moieties to CD206 expressing cells in target tissues, such as tumors or other sites of inflammation.

Abstract: Provided are compounds, compositions, and methods of repolarizing a tumor associated macrophage (TAM), reducing macrophage-mediated inflammation, and treating a disease. A compound or pharmaceutical composition may be administered to a subject in need thereof, where the compound comprises a polymeric carbohydrate backbone, one or more mannose-binding C-type lectin receptor targeting moieties, and a therapeutic agent comprises one or more reactive hydroxyl groups and coupled to the polymeric carbohydrate backbone via a degradable linker. The degradable linker may comprise one or more carbonate and/or disulfide moieties. The disease to be treated may include cancer, an autoimmune disease, an inflammatory disorder, Non-Alcoholic Steatohepatitis (NASH), acute respiratory distress syndrome (ARDS), sepsis, coronavirus infection, influenza infection, cytokine storms, and other macrophage involved diseases.

Abstract: Provided are compounds, compositions, methods, and kits for increasing target specificity of a mannosylated carbohydrate polymeric therapeutic or diagnostic compound to reduce or eliminate localization of the mannosylated carbohydrate polymeric therapeutic or diagnostic compound to off-target sites. Mannosylated carbohydrate polymers are synthesized to be modified to be either polyanionic (i.e., net negatively charged) or electrostatically neutral, and using these polyanionic or neutral mannosylated carbohydrate polymers as competitors for polycationic (i.e., net positively charged) mannosylated carbohydrate polymers carrying small molecule drug payloads or imaging moieties to CD206 expressing cells in target tissues, such as tumors or other sites of inflammation.

Abstract: Provided are novel compounds containing a polymeric carbohydrate backbone, one or more mannose-binding C-type lectin receptor targeting moieties, and a nitrogenous bisphosphonate compound coupled to the backbone via a thiol-maleimide conjugation, in addition to pharmaceutical compositions, methods of synthesizing, and methods of use. The thiol-maleimide conjugation of a bisphosphonate to a polymeric carbohydrate backbone provides for methods of using the compounds and compositions thereof for releasing the therapeutic payload when internalized into a mannose-binding C-type lectin receptor-expressing cell, such as tumor associated macrophages (TAMs) for the treatment of various diseases, including, cancer, autoimmune diseases, and inflammatory disorders.

Abstract: Provided are compounds, compositions, methods, and kits for increasing target specificity of a mannosylated carbohydrate polymeric therapeutic or diagnostic compound to reduce or eliminate localization of the mannosylated carbohydrate polymeric therapeutic or diagnostic compound to off-target sites. Mannosylated carbohydrate polymers are synthesized to be modified to be either polyanionic (i.e., net negatively charged) or electrostatically neutral, and using these polyanionic or neutral mannosylated carbohydrate polymers as competitors for polycationic (i.e., net positively charged) mannosylated carbohydrate polymers carrying small molecule drug payloads or imaging moieties to CD206 expressing cells in target tissues, such as tumors or other sites of inflammation.