title: Herceptin-conjugated temperature-sensitive immunoliposomes encapsulating gemcitabine for breast cancer.
abstract: Gemcitabine (2',2'-difluorodeoxycytidine, GCT) is an analog of deoxycytidine with cytotoxicity for breast cancer cells. However, because of its hepatotoxicity and other side effects, an efficient drug delivery system is needed for better therapeutic outcomes. A temperature-sensitive PEGylated immunoliposome (TSL) with trastuzumab (or Herceptin) attached encapsulating GCT (Her-PEG-TSL-GCT) was prepared. The mean diameter of the liposome was about 200 nm and the prepared immunoliposome showed the capacity to deliver the payload to the hyperthermic environment. The actual number of antibody molecules attached to one single liposome is about 19, with the GCT encapsulation efficiency of 54.6 ± 3.50 %. This immunoliposome shows a temperature-dependent drug release at around 41-43 °C. Anticancer activity of Her-PEG-TSL-GCT was determined using HER-2 expressing breast cancer cells, SK-BR-3, in vitro and resulted in increased cytotoxicity compared to free GCT (IC20 11.7 nM) or conventional liposome lacking the targeting antibody. In conclusion, these data show that improved delivery of GCT to breast cancer cells can be achieved by Her-PEG-TSL-GCT in vitro, and this strategy could be used for breast cancer therapy with further studies.
authors.affiliation: Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women's University Chungpa-Dong 2-Ga, Yongsan-Gu, Seoul, 140-742, Korea.|Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI, 53705-2222, USA.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women's University Chungpa-Dong 2-Ga, Yongsan-Gu, Seoul, 140-742, Korea.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Koo
authors.affiliation: Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women's University Chungpa-Dong 2-Ga, Yongsan-Gu, Seoul, 140-742, Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women's University Chungpa-Dong 2-Ga, Yongsan-Gu, Seoul, 140-742, Korea. jsk9574@sm.ac.kr.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000276:immunology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature; D000068878:Trastuzumab / Q000737:chemistry* / Q000276:immunology*; D000093542:Gemcitabine
chemical_list: D008081:Liposomes; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D000068878:Trastuzumab; D000093542:Gemcitabine
keywords: Breast cancer; Gemcitabine; Herceptin; Immunoliposomes; Targeting