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

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