title: Trastuzumab-cisplatin conjugates for targeted delivery of cisplatin to HER2-overexpressing cancer cells.
abstract: Cisplatin is widely used for the treatment of numerous types of cancer, while its application is limited by the adverse side effects for its poor selectivity. Trastuzumab is a highly targeting protein to HER2 protein, and it is usually combined with paclitaxel or cisplatin for the treatment of HER2-overexpressing breast cancer. In the present work, we used trastuzumab as a targeting carrier for platinum drug delivery. In ELISA assays and immunofluorescence study, Tmab-1 exhibited high and specific binding affinity to HER2 protein and HER2-overexpressing SK-BR-3 cells. In cytotoxicity test, Tmab-1 showed promising antiproliferative activity to SK-BR-3 cells, while it hardly inhibited the growth of MCF-7 cells and MDA-MB-231 cells. The cell cycle arrest study showed Tmab-1 induced the cell cycle arrest mainly at G2/M phase. This work indicates that trastuzumab is an effective and potential targeting carrier for drug delivery.
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210089, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210089, PR China.
authors.forename: Qiucui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Antibody Technique of Ministry of Health, School of Pathology, Nanjing Medical University, Nanjing 210093, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210089, PR China. Electronic address: chmsunbw@seu.edu.cn.
authors.forename: Baiwang
authors.initials: B
authors.lastname: Sun
mesh_terms: D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D002945:Cisplatin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D011485:Protein Binding / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab / Q000494:pharmacology*
chemical_list: D002945:Cisplatin; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: Platinum drug; Targeting delivery; Trastuzumab