title: SM5-1-conjugated PLA nanoparticles loaded with 5-fluorouracil for targeted hepatocellular carcinoma imaging and therapy.
abstract: SM5-1 is a humanized mouse antibody which has a high binding specificity for a membrane protein of about 230 kDa overexpressed in hepatocellular carcinoma (HCC), melanoma and breast cancer. In this study, SM5-1-conjugated poly D, L (lactide-coglycolide) (PLA) PLA containing Cy7 (PLA-Cy7-SM5-1) was prepared to study the targeting specificity of the bioconjugate to HCC-LM3-fLuc cell. Then, SM5-1-conjugated PLA containing 5-fluorouracil (5-FU) (PLA-5FU-SM5-1) and PLA containing 5-FU (PLA-5FU) were prepared for treatment of subcutaneous HCC-LM3-fLuc tumor mice. The results showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 45.07%, 23.56% and 19.05% tumor growth inhibition rate, respectively, on day 31 post-treatment as determined by bioluminescent intensity. In addition, in order to evaluate the antitumor efficacy of PLA-5FU-SM5-1, HCC-LM3-fLuc cells were injected into the liver to establish the experimental orthotopic liver tumor models. The experiments showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 53.24%, 31.00%, and 18.11% tumor growth inhibition rate, respectively, on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, we have calculated the three-dimensional location of the liver cancer in mice using a multilevel adaptive finite element algorithm based on bioluminescent intensity decay calibration. The reconstruction results demonstrated that PLA-5FU-SM5-1 inhibited the tumor rapid progression, which were consistent with the results of subcutaneous tumor mice experiments and in vitro cell experiment results.
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Xibo
authors.initials: X
authors.lastname: Ma
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, California 94305-5344, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Nanomedicine and Biosensor Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
authors.forename: Yushen
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: jie.tian@ia.ac.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D005472:Fluorouracil
keywords: Bioluminescence imaging (BLI); Bioluminescent tomography (BLT); Nanoparticles; Targeted imaging and therapy