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Folate-containing dextran ligand (FA-Dextran-DTPA) was synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and folate (FA) as a tumor-targeting group into dextran as a polymer carrier. This ligand was further reacted with gadolinium chloride to make a dextran gadolinium complex FA-Dextran-DTPA-Gd. The ligand and its gadolinium complex were characterized by H-NMR, FTIR, UV-Vis, average particle sizes and zeta potential, as well. In vitro properties including relaxivity, cytotoxicity assay, cellular uptake assay, and magnetic resonance imaging (MRI) were also evaluated. Compared with Gd-DTPA, FA-Dextran-DTPA-Gd possessed obviously higher relaxation effectiveness and lower cytotoxicity to HeLa cells. FA-Dextran-DTPA-Gd had a high affinity to the H460 and MDA-MB-231 tumor cells and can be taken up selectively by these tumor cells. Moreover, FA-Dextran-DTPA-Gd showed enhanced signal intensities (SI) of MRI and enhanced the contrast of MR images of tumor cells. These results indicated that FA-Dextran-DTPA-Gd showed the potential as a tumor-targeting contrast agent in MRI. [ABSTRACT FROM AUTHOR]

Abstract: Porphyrin-containing polyaspartamide ligands (APTSPP–PHEA–DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4′-aminophenyl)-10,15,20-tris(4′-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP–PHEA–DTPA–Gd). Experimental data of 1H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP–PHEA–DTPA–Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd–DTPA. Moreover, APTSPP–PHEA–DTPA–Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. [Copyright &y& Elsevier]