DataVXAdvanced MaterialsPaper
journal article·2023-12Open access

Brain‐Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha‐Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease

Mor Sela, Maria Poley, Patricia Mora‐Raimundo, Shaked Kagan, Aviram Avital, Maya Kaduri, Gal Chen, Omer Adir, Adi Rozencweig, Yfat Weiss, Ofir Sade, Yael Leichtmann‐Bardoogo, Lilach Simchi, Shlomit Aga‐Mizrachi, Batia Bell, Yoel Yeretz‐Peretz, Aviv Zaid Or, Ashwani Choudhary, Idan Rosh, Diogo Cordeiro, Stav Cohen‐Adiv, Yevgeny Berdichevsky, Anas Odeh, Jeny Shklover, Janna Shainsky‐Roitman, Joshua E. Schroeder, Dov Hershkovitz, Peleg Hasson, Avraham Ashkenazi, Shani Stern, Tal Laviv, Ayal Ben‐Zvi, Avi Avital, Uri Ashery, Ben M. Maoz, Avi Schroeder

Advanced Materials· Volume 35· Issue 51
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Abstract

Abstract Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain‐targeted liposomes (BTL) enhance the delivery of mAbs across the blood‐brain‐barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin‐receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha‐synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100‐nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.
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Research context

Nanomaterials

OpenAlex topics: Neurological disorders and treatments · Parkinson's Disease Mechanisms and Treatments · Neuroscience and Neural Engineering

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies Department of Chemical Engineering Technion ‐ Israel Institute of Technology Haifa 32000 Israel

The Norman Seiden Multidisciplinary Program for Nanoscience and Nanotechnology Technion ‐ Israel Institute of Technology Haifa 32000 Israel

The Interdisciplinary Program for Biotechnology Technion – Israel Institute of Technology Haifa 32000 Israel

School of Neurobiology Biochemistry and Biophysics George S. Wise Faculty of Life Sciences Sagol School of Neuroscience Tel Aviv University Tel Aviv 6997801 Israel

Sagol School of Neuroscience Tel Aviv University Tel Aviv 6997801 Israel

Department of Occupational Therapy Faculty of Social Welfare and Health Sciences University of Haifa Haifa 3498838 Israel

Department of Developmental Biology and Cancer Research The Institute for Medical Research Israel‐Canada, Faculty of Medicine The Hebrew University of Jerusalem Jerusalem 9190500 Israel

Department of Physiology and Pharmacology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 Israel

Sagol Department of Neurobiology Faculty of Natural Sciences University of Haifa Haifa 3498838 Israel

The Department of Cell and Developmental Biology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 Israel

Department of Genetics and Developmental Biology The Rappaport Faculty of Medicine and Research Institute Technion – Israel Institute of Technology Haifa 32000 Israel

Spine Unit Orthopedic Complex Hadassah Hebrew University Medical Center Kiryat Hadassah, POB 12000, Jerusalem 9190500 Israel

Department of Pathology Tel Aviv Sourasky Medical Center Tel Aviv 6997801 Israel

Sackler Faculty of Medicine Tel Aviv University Tel Aviv 6997801 Israel

Department of Biomedical Engineering Tel Aviv University Tel Aviv 6997801 Israel

The Center for Nanoscience and Nanotechnology Tel Aviv University Tel Aviv 6997801 Israel

Sagol Center for Regenerative Medicine Tel Aviv University Tel Aviv 6997801 Israel

Funding

Israel National Institute for Health Policy Research · Michael J. Fox Foundation for Parkinson's Research · Teva Pharmaceutical Industries · Phospholipid Research Center · Israel Science Foundation

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