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

  • Eur J Pharm Biopharm. 2021 Jan;158:390-400. doi: 10.1016/j.ejpb.2020.12.012.
Mohamad Alawak  1 ,  Alice Abu Dayyih  1 ,  Gihan Mahmoud  2 ,  Imran Tariq  3 ,  Lili Duse  1 ,  Nathalie Goergen  1 ,  Konrad Engelhardt  1 ,  Shashank Reddy Pinnapireddy  1 ,  Jarmila Jedelská  1 ,  Muhannad Awak  4 ,  Alexander M König  5 ,  Jana Brüßler  1 ,  Jörg W Bartsch  6 ,  Udo Bakowsky  7
Affiliations
  • 1. Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany.
  • 2. Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Ain Helwan, 11795 Cairo, Egypt.
  • 3. Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany; Punjab University College of Pharmacy, University of the Punjab, 54000 Lahore, Pakistan.
  • 4. Department of Neurosurgery, Wolfsburg Hospital, 38440 Wolfsburg, Germany.
  • 5. Department of Diagnostic and Interventional Radiology, University of Marburg, 35032 Marburg, Germany.
  • 6. Department of Neurosurgery, University of Marburg, University Hospital Marburg, 35032 Marburg, Germany.
  • 7. Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany. Electronic address: [email protected].
PMID: 33338603 DOI: 10.1016/j.ejpb.2020.12.012
Abstract

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 (LipTS-GD) could specifically increase the intracellular accumulation of cytotoxic drugs. The surface of doxorubicin-loaded LipTS-GD was modified by covalent coupling of MAB1031 antibody (LipTS-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 LipTS-GD-MAB treatment caused a higher cytotoxic effect at the cellular target site.

Keywords
ADAM8 Targeting; Diagnostic; Doxorubicin; Drug Delivery; Magnetic Resonance Imaging; Thermosensitive Liposomes.
Products