Ling Rong1,2, Shuping Zhou3, Xinkuang Liu3, Amin Li3, Tao Jing2, Xueke Liu2, Yinci Zhang2, Shiyu Cai2, Xiaolong Tang1,2. 1. a Bozhou People's Hospital Affiliated to Medical College , Anhui University of Science & Technology , Bozhou , China. 2. b Medical College , Anhui University of Science & Technology , Huainan , China. 3. c Huainan First People's Hospital and First Affiliated Hospital of Medical College , Anhui University of Science & Technology , Huainan , China.
Abstract
BACKGROUND: Emtansine (DM1) is a highly potent anti-microtubule agent that has shown promising results for breast cancer treatment, but side effects limit its widespread clinical use. In this research, a new nano-drug was developed to integrate DM1 agent with antibody targeting. METHODS: A system of novel nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti-HER2 antibody, Herceptin®, Trastuzumab) was developed for HER2+ breast cancer treatment, and its physical characterization and antitumor biological activity were investigated. RESULTS: DM1-NPs-Tmab-targeted HER2+ breast cancer cells specifically were developed. Compared with naked DM1 and Herceptin, DM1-NPs-Tmab showed greater toxicity on HER2+ cancer cells and blocked the HER2-PI3K/Akt cell activation pathway. DM1-NPs-Tmab inhibited tumor growth by 88% and had less toxic effects in vivo than non-targeting DM1 when administered to MDA-MB-453 xenograft bearing mice. CONCLUSION: DM1-NPs-Tmab shows superior anti-tumor efficacy than free Herceptin or DM1. DM1-NPs-Tmab is a potential promising formulation for targeting biotherapy of HER2+ tumors.
BACKGROUND:Emtansine (DM1) is a highly potent anti-microtubule agent that has shown promising results for breast cancer treatment, but side effects limit its widespread clinical use. In this research, a new nano-drug was developed to integrate DM1 agent with antibody targeting. METHODS: A system of novel nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti-HER2 antibody, Herceptin®, Trastuzumab) was developed for HER2+ breast cancer treatment, and its physical characterization and antitumor biological activity were investigated. RESULTS:DM1-NPs-Tmab-targeted HER2+ breast cancer cells specifically were developed. Compared with naked DM1 and Herceptin, DM1-NPs-Tmab showed greater toxicity on HER2+ cancer cells and blocked the HER2-PI3K/Akt cell activation pathway. DM1-NPs-Tmab inhibited tumor growth by 88% and had less toxic effects in vivo than non-targeting DM1 when administered to MDA-MB-453 xenograft bearing mice. CONCLUSION:DM1-NPs-Tmab shows superior anti-tumor efficacy than free Herceptin or DM1. DM1-NPs-Tmab is a potential promising formulation for targeting biotherapy of HER2+ tumors.
Entities:
Keywords:
Emtansine (DM1); HER2+ tumors; drug delivery; targeting nanoparticles
Authors: Colin T Huang; Xin Guo; Cyril Bařinka; Shawn E Lupold; Martin G Pomper; Kathleen Gabrielson; Venu Raman; Dmitri Artemov; Sudath Hapuarachchige Journal: Mol Pharm Date: 2020-08-17 Impact factor: 4.939
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