title: DNA-affibody nanoparticles for inhibiting breast cancer cells overexpressing HER2.
abstract: In this study, we have prepared a DNA-affibody nanoparticle which mimics a antibody in its ability to specifically target the HER2 receptor. This nanoparticle has a smaller size (95 kDa) than the monoclonal antibody, trastuzumab (150 kDa) and at least two-fold greater activity toward BT474 cells than trastuzumab. The DNA in this nanoparticle structure has two functions, namely as a support to anchor two affibody molecules and as a vehicle to non-covalently bind multiple copies of a small molecule drug for drug delivery. Each DNA-affibody nanoparticle can bind ∼53 molecules of doxorubicin (DOX) to form a complex, which exhibits greater selectivity toward and inhibition of breast cancer cells overexpressing HER2 than doxorubicin does. As expected, the nanoparticle exhibits lesser inhibition of cells expressing HER2 at a low level. Thus, the nanoparticle represents a highly efficacious agent for inhibiting cancer cells which overexpress HER2, but with low toxicity toward normal cells.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China and Biodesign Center for BioEnergetics, Arizona State University, Tempe 85287, USA. Shengxi.Chen.1@asu.edu.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biodesign Center for BioEnergetics, Arizona State University, Tempe 85287, USA. Shengxi.Chen.1@asu.edu.
authors.forename: Shuoxing
authors.initials: S
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Biodesign Center for BioEnergetics, Arizona State University, Tempe 85287, USA. Shengxi.Chen.1@asu.edu.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Bai
authors.affiliation: Biodesign Center for BioEnergetics, Arizona State University, Tempe 85287, USA. Shengxi.Chen.1@asu.edu.
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
authors.affiliation: Biodesign Center for BioEnergetics, Arizona State University, Tempe 85287, USA. Shengxi.Chen.1@asu.edu.
authors.forename: Shengxi
authors.identifier: 0000-0001-7493-6985
authors.initials: S
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004247:DNA; D004317:Doxorubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human