HER-2-mediated nano-delivery of molecular targeted drug potently suppresses orthotopic epithelial ovarian cancer and metastasis
The treatment of epithelial ovarian cancer (EOC) has made slow progress due to absence of effective adjuvant chemotherapy that is capable of preventing tumor relapse and metastasis. Molecular targeted drugs such as PARP and PLK1 inhibitors appear to be promising new treatments for EOC. The low EOC cell uptake, poor selectivity and pronounced toxicity, however, greatly compromise their clinical efficacy. Herein, we report that HER-2-mediated nano-delivery of clinical PLK1-targeted drug, volasertib (Vol), while causing little toxicity potently suppresses orthotopic EOC and metastasis. Anti-HER-2 antibody, trastuzumab (Tra), was conjugated onto Vol-loaded polymersomes via click chemistry yielding Tra-PVol with a size of 33 nm and optimally about 5 Tra per polymersome. Tra-PVol exhibited clearly stronger uptake and anti-tumor activity (IC