Polymer-lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells

• Published in: International journal of nanomedicine 2017-01, Vol.12, p.6909-6921
• Main Authors: Li, Jun, Xu, Wenqing, Yuan, Xiaoli, Chen, Huaiwen, Song, Hao, Wang, Bingquan, Han, Jun
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Aqueous solutions; Biocompatibility; Biomedical materials; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer cells; Cancer metastasis; Cancer stem cells; Cancer therapies; Cell Line, Tumor; Cytotoxicity; Dehydrogenases; Drug delivery systems; Drug Delivery Systems - methods; Female; Health aspects; HER2; Humans; Lipids; Lipids - chemistry; Liver cancer; Metastasis; Mice; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Original Research; Polyethylene glycol; Polymers; Polymers - chemistry; Pyrans - administration & dosage; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - immunology; Receptor, ErbB-2 - metabolism; Salinomycin; Stem cells; Tumorigenesis; Xenograft Model Antitumor Assays
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S144184

Breast cancer stem cells (CSCs) are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer-lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2) to target both HER2-positive breast CSCs and cancer cells. The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer-lipid salinomycin nanoparticles was evaluated in vitro and in vivo. Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone. Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells.