ADAM 8 as a novel target for doxorubicin delivery to TNBC cells using magnetic thermosensitive liposomes

Metastatic breast cancer is one of the most common causes of cancer-related death in women worldwide. The transmembrane metalloprotease-disintegrin (ADAM8) protein is highly overexpressed in triple-negative breast cancer (TNBC) cells and potentiates tumor cell invasion and extracellular matrix remodeling. Exploiting the high expression levels of ADAM8 in TNBC cells by delivering anti-ADAM8 antibodies efficiently to the targeted site can be a promising strategy for therapy of TNBC. For instance, a targeted approach with the aid of ultra-high field magnetic resonance imaging (UHF-MRI) activatable thermosensitive liposomes (Lip(TS-GD)) could specifically increase the intracellular accumulation of cytotoxic drugs. The surface of doxorubicin-loaded Lip(TS-GD) was modified by covalent coupling of MAB1031 antibody (Lip(TS-GD-MAB)) in order to target the overexpressed ADAM8 in ADAM8 positive MDA-MB-231 cells. Physicochemical characterization of these liposomes was performed using size, surface morphology and UHF-MRI imaging analysis. In vitro cell targeting was investigated by the washing and circulation method. Intracellular trafficking and lysosomal colocalization were assessed by fluorescence microscopy. Cell viability, biocompatibility and in-ovo CAM assays were performed to determine the effectiveness and safety profiles of liposome formulations. Our results show specific binding and induction of doxorubicin release after Lip(TS-GD-MAB) treatment caused a higher cytotoxic effect at the cellular target site.

Automated summary

The overexpression of ADAM8 in TNBC cells can be exploited for targeted therapy, with specific drug delivery resulting in increased intracellular accumulation and enhanced cytotoxic effects at the cellular target site.