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

Abstract

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-^99mTc were successfully synthesized and characterized. Poly(N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid conjugate 3, diethylenetriaminepentaacetic acid-^99mTc, and poly(N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid-^99mTc were also synthesized and characterized for comparison (^99mTc: 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-^99mTc (4.82%ID/g ± 0.46%ID/g (percentage injected dose per gram tissue)) compared with poly(N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid-^99mTc (2.69%ID/g ± 0.15%ID/g) and diethylenetriaminepentaacetic acid-^99mTc (0.83%ID/g ± 0.03%ID/g). Moreover, higher tumor/organ ratios for poly(N-(2-hydroxypropyl)methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid-^99mTc 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.

Keywords

N-(2-hydroxypropyl)methacrylamide copolymers targeted delivery sulfamethazine biodistribution hepatocellular carcinoma macromolecular targeting carrier

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