Synthesis, characterization, and in vivo evaluation of tumor targeting N-(2-hydroxypropyl) methacrylamide copolymer conjugates containing sulfamethazine groups

Recent studies have identified that sulfadiazine derivatives can be concentrated in the hepatocellular carcinoma tissue. Herein, we report the synthesis, characterization, and evaluation of a novel sulfamethazine N-(2-hydroxypropyl)methacrylamide copolymer conjugates for tumor targeting. N-(3-Aminopropyl)methacrylamide-diethylenetriaminepentaacetic acid monomer 1, methacryloyl-sulfamethazine monomer 2, poly(N-(2-hydroxypropyl) methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid conjugate 4, and poly(N-(2-hydroxypropyl) methacrylamide)sulfamethazine- diethylenetriaminepentaacetic acid-Tc-99m were successfully synthesized and characterized. Poly(N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid conjugate 3, diethylenetriaminepentaacetic acid-Tc-99m, and poly(N-(2-hydroxypropyl) methacrylamide)-diethylenetriaminepentaacetic acid-Tc-99m were also synthesized and characterized for comparison (Tc-99m: metastable technetium-99). A 24-h necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(N-(2-hydroxypropyl) methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid-Tc-99m (4.82%ID/g +/- 0.46%ID/g (percentage injected dose per gram tissue)) compared with poly(N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid-Tc-99m (2.69% ID/g +/- 0.15%ID/g) and diethylenetriaminepentaacetic acid-Tc-99m (0.83%ID/g +/- 0.03%ID/g). Moreover, higher tumor/organ ratios for poly(N-(2-hydroxypropyl) methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid-Tc-99m indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly(N-(2-hydroxypropyl) methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid can potentially be used as a macromolecular targeting carrier for hepatocellular carcinoma in mice.