Trastuzumab-cisplatin conjugates for targeted delivery of cisplatin to HER2-overexpressing cancer cells |
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| Affiliation: | 1. School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210089, PR China;2. Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland;3. Key Laboratory of Antibody Technique of Ministry of Health, School of Pathology, Nanjing Medical University, Nanjing 210093, PR China;1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;2. Department of Pharmacy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China;3. Department of Pharmacy, Zengcheng People’s Hospital (Boji-affiliated Hospital of Sun Yat-sen University), Guangzhou, Guangdong, China;4. Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China;1. Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China;2. Department of Clinical Laboratory, The second Hospital of Shandong University, Jinan, Shandong, 250033, China;1. Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan;2. Department of Oncology Center, Osaka University School of Medicine, Suita, Osaka, Japan;3. Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan;4. AMED-CREST, Suita, Osaka, Japan |
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| 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. |
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| Keywords: | Targeting delivery Trastuzumab Platinum drug |
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