title: Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer.
abstract: Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T(1) relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies, the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors.
authors.affiliation: School of Pharmaceutical Science, Shandong University, Ji'nan, People's Republic of China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Chen
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Lu
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D019786:Gadolinium DTPA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008422:Materials Testing; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D003287:Contrast Media; D004337:Drug Carriers; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D019786:Gadolinium DTPA