2. Academic Validation
  3. ADAM 8 as a novel target for doxorubicin delivery to TNBC cells using magnetic thermosensitive liposomes

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

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.

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