Combination of targeted daunorubicin liposomes and targeted emodin liposomes for treatment of invasive breast cancer

Abstract

Conventional treatment fails to completely eliminate highly invasive breast cancer cells, and most surviving breast cancer cells tend to reproliferate and metastasize by forming vasculogenic mimicry (VM) channels. Thus, a type of targeted liposomes was developed by modification with arginine₈–glycine–aspartic acid (R₈GD) to encapsulate daunorubicin and emodin separately. A combination of the two targeted liposomes was then developed to destroy VM channels and inhibit tumour metastasis. MDA-MB-435S cells, a highly invasive breast cancer, were then evaluated in vitro and in mice. The experiments indicated that R₈GD modified daunorubicin liposomes plus R₈GD modified emodin liposomes had small particle size, uniform particle size distribution and high drug encapsulation rate. The combination of the two targeted liposomes exerted strong toxicity on the MDA-MB-435S cells and effectively inhibited the formation of VM channels and the metastasis of tumour cells. Action mechanism studies showed that the R₈GD modified daunorubicin liposomes plus R₈GD modified emodin liposomes could downregulate some metastasis-related proteins, including MMP-2, VE-cad, TGF-β1 and HIF-1α. These studies also demonstrated that the targeted liposomes allowed the chemotherapeutic drug to selectively accumulate at tumour site, thus exhibiting a distinct antitumor effect. Therefore, the combination of targeted daunorubicin liposomes and targeted emodin liposomes can provide a potential treatment for invasive breast cancer.

Keywords:

• R₈GD
• daunorubicin
• emodin
• vasculogenic mimicry channels
• tumour metastasis

Disclosure statement

The authors report no conflict of interest in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81874347 and 81673603) and LiaoNing Revitalization Talents Program (Grant No. XLYC1807132).