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Trastuzumab-modified DM1-loaded nanoparticles for HER2 + breast cancer treatment: an in vitro and in vivo study.
Artificial Cells, Nanomedicine, and Biotechnology 2017 October 26
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.
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.
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