Related Experiment Video
Updated: Nov 25, 2025
Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
Published on: November 1, 2017
ADAM 8 as a novel target for doxorubicin delivery to TNBC cells using magnetic thermosensitive liposomes
Mohamad Alawak1, Alice Abu Dayyih1, Gihan Mahmoud2
1Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany.
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.
Insights
Targeted therapy using MAB1031 antibody-conjugated liposomes effectively delivered doxorubicin to ADAM8-overexpressing triple-negative breast cancer cells, enhancing cytotoxicity. This approach shows promise for treating metastatic breast cancer.
Area of Science:
- Oncology
- Nanomedicine
- Biochemistry
Background:
- Metastatic breast cancer, particularly triple-negative breast cancer (TNBC), is a significant cause of cancer mortality.
- ADAM8 protein is overexpressed in TNBC, promoting tumor invasion and extracellular matrix remodeling.
- Targeting ADAM8 offers a potential therapeutic strategy for TNBC.
Purpose of the Study:
- To develop and evaluate antibody-targeted thermosensitive liposomes for delivering doxorubicin to ADAM8-positive TNBC cells.
- To investigate the physicochemical properties, in vitro targeting, and therapeutic efficacy of the novel liposome formulation.
Main Methods:
- Doxorubicin-loaded thermosensitive liposomes (LipTS-GD) were surface-modified with MAB1031 antibody (LipTS-GD-MAB) for ADAM8 targeting.
- Physicochemical characterization included size, morphology, and UHF-MRI analysis.
- In vitro studies assessed cell targeting, intracellular trafficking, lysosomal colocalization, cell viability, and biocompatibility.
Main Results:
- LipTS-GD-MAB demonstrated specific binding to ADAM8-positive MDA-MB-231 cells.
- The targeted liposomes facilitated doxorubicin release and enhanced intracellular accumulation.
- LipTS-GD-MAB treatment resulted in significant cytotoxicity and showed favorable safety profiles in biocompatibility assays.
Conclusions:
- Antibody-conjugated thermosensitive liposomes are effective in targeting ADAM8-expressing TNBC cells.
- This targeted drug delivery system enhances the cytotoxic effect of doxorubicin at the tumor site.
- The developed liposomal formulation holds potential as a therapeutic strategy for metastatic breast cancer.
More Related Videos
09:01Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy
Published on: May 22, 2020
13:41Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model
Published on: January 13, 2023
