Camouflaged liposomes by 11A4-nanobody for co-delivery of cisplatin and nitroxoline in breast cancer tumors: An in vitro/in vivo study

Abstract

Nitroxoline (NIT) is a quinoline antibiotic with anti-cancer effects which prevents cell migration by inhibition of cathepsin B enzyme. Cisplatin (CIS) is normally used for various kinds of malignancies such as metastatic breast cancer. The goal of the present study was increasing cellular toxicity and cell migration inhibition by co-delivery of NIT-CIS using targeted liposomes by anti HER2 nanobody. Liposomes were prepared by solvent injection method using cholesterol, soy lecithin and maleimide-polyethylene glycol 2000 distearoyl phosphatidyl ethanolamine (Mal-PEG-DSPE) and targeted by anti HER2 nanobody. The liposomes were optimized for their particle size, zeta potential, drugs loading and release efficiency. Then their cytotoxicity, migration, cellular uptake and apoptosis induction were tested on TUBO (HER2(+)) and MDA-MB-213 (HER2(-)) cell lines. The in vivo antitumor activity of CIS-NIT loaded in targeted liposomes was compared with free drugs solution and non-targeted liposomes in TUBO cells induced breast cancer in Balb-c mice. Results indicated that the mixture of CIS and NIT significantly increased cytotoxicity. Moreover, targeted liposomes increased cellular toxicity and cellular uptake in TUBO cells, unlike MDA-MB-213 cells. Cell migration studies implied the effect of NIT combinations on lowering the invasiveness of the cells. Targeted liposomes loaded with CIS-NIT had outstanding tumor suppression efficiency compared to control group, non-targeted liposomes and free drugs.