The present invention concerns aminobenzylguanidine derivative ligands specifically targeting neuroblastoma cells with an improved cellular uptake. The improved cellular uptake provides for the therapeutic and diagnostic use of the ligands in neuroblastoma-related diseases.
1. Claims 1. A ligand compound having the formula: <img class="EMIRef" id="605617329-imgf000038-0001" /> wherein Xi is an amide bond; X<2>is independently an amide bond and, together with the benzylguanidine attached to it, is absent or present; Ri is an optionally substituted chain containing stable linkages, such as amide bonds, thioamide bonds, carbamate bonds, thiocarbamate bonds, carbon-carbon bonds, ether bonds, sulfide bonds, and/or amine bonds, carbon, nitrogen and/or oxygen atoms in the chain, and having a chain length of 3 to 50, preferably 18 to 40 atoms, such as 21 to 35 atoms, e.g. 22 to 30 atoms; Ri does not contain any conjugated double bonds; and the benzylguanidine groups are in the meta and/or para position to Xi and X<2>, respectively. 2. The ligand compound according to claim 1, wherein Ri does not contain any carbon-carbon double bonds. 3. The ligand compound according to any one of claims 1 to 2, wherein Ri is a chain containing Ci to C<4>alkanediyl moieties connected by amide bonds, thioamide bonds, carbamate bonds, thiocarbamate bonds, sulfide bonds and/or ether bonds. 4. The ligand compound according to claim 3, wherein Ri is a chain containing Ci to C<4>alkanediyl moieties connected by amide bonds and/or thioamide bonds, and wherein Ri is optionally substituted with amino groups, carboxylic acid groups, and/or thiocarboxylic acid groups. 5. The ligand compound according to claim 4, wherein Ri is a chain containing Ci to C<4>alkanediyl moieties connected by amide bonds, and wherein Ri is optionally substituted with amino groups and/or carboxylic acid groups. 6. The ligand compound according to any one of claims 1 to 5, wherein X<2>, together with the benzylguanidine attached to it, is present. 7. The ligand compound according to any one of claims 1 to 6, wherein the guanidine groups are in the para position to Xi and X<2>. 8. A conjugate compound comprising a ligand compound according to any one of claims 1 to 7, wherein an Active is attached to Ri, optionally via a linker, the conjugate compound having the formula: Active— (linker) <img class="EMIRef" id="605617329-imgf000039-0001" /> wherein the linker may be absent or present and has a molecular weight in the range 50 to 10000 Da and is linked to Ri by a stable linkage, such as an amide bond, a carbamate bond, a carbon-carbon bond, an ether bond, or an amine bond; the Active is an active pharmaceutical ingredient, an immunostimulant, a contrast agent, a fluorophore, a nanoparticle loaded with an active pharmaceutical ingredient, an immunostimulant, a contrast agent, and/or a fluorophore; and the Active is attached to the linker, if present, via a stable linkage, such as an amide bond, a thioamide bond, a carbamate bond, a thiocarbamate bond, a carbon-carbon bond, an ether bond, a sulfide bond, or an amine bond . 9. The conjugate compound according to claim 8, wherein the Active is a nanoparticle loaded with an active pharmaceutical ingredient, an immunostimulant, a contrast agent, and/or a fluorophore. 10. The conjugate compound according to claim 9, wherein the nanoparticle is a mesoporous silica nanoparticle, a polymeric nanoparticle, such as a biodegradable polymeric nanoparticle, a liposome, a metallic nanoparticle, or a viral nanoparticle. 11. The conjugate compound according to claim 8, wherein the Active is an active pharmaceutical ingredient, an immunostimulant, a contrast agent, and/or a fluorophore. 12. The conjugate compound according to any one of claims 8 to 11, wherein the linker is polyethylene glycol. 13. The conjugate compound according to claim 11, wherein the linker is absent and the Active therefore is linked directly to Ri. 14. The conjugate compound according to any one of claims 8 to 13, wherein the Active is an active pharmaceutical ingredient, an immunostimulant, or a nanoparticle loaded with an active pharmaceutical ingredient or an immunostimulant for use in a method of treating neuroblastoma. 15. The conjugate compound according to any one of claims 8 to 13, wherein the Active is a contrast agent or a fluorophore, or a nanoparticle loaded with a contrast agent or a fluorophore for use in a method of diagnosis.