Liposomal Carrier Conjugated to APP-Derived Peptide for Brain Cancer Treatment
- PDF / 2,347,124 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 88 Downloads / 183 Views
ORIGINAL RESEARCH
Liposomal Carrier Conjugated to APP‑Derived Peptide for Brain Cancer Treatment Martin Gabay1 · Abraham Weizman2,3 · Nidal Zeineh1 · Meygal Kahana1 · Fadi Obeid1 · Nahum Allon1 · Moshe Gavish1 Received: 30 June 2020 / Accepted: 22 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Brain tumors are hard to treat with the currently available therapy. The major obstacle in the treatment of brain tumors is the lack of therapeutic strategies capable to penetrate the blood–brain barrier (BBB). The BBB is an endothelial interface that separates the brain from the circulatory blood system and prevents the exposure of the central nervous system (CNS) to circulating toxins and potentially harmful compounds. Unfortunately, the BBB prevents also the penetration of therapeutic compounds into the brain. We present here a drug-delivery liposomal carrier, conjugated to a peptide inserted in the liposomal membrane, which is putatively recognized by BBB transporters. The peptide is a short sequence of 5 amino acids (RERMS) present in the amyloid precursor protein (APP). This APP-targeted liposomal system was designed specifically for transporting compounds with anti-cancer activity via the BBB into the brain in an effective manner. This drug-delivery liposomal carrier loaded with the anti-cancer compounds temozolomide (TMZ), curcumin, and doxorubicin crossed the BBB in an in vitro model as well as in vivo (mice model). In the in vitro model, the targeted liposomes crossed the BBB model fourfold higher than the non-targeted liposomes. Labeled targeted liposomes penetrated the brain in vivo 35% more than non-targeted liposomes. Treatment of mice that underwent intracranial injection of human U87 glioblastoma, with the targeted liposomes loaded with the three tested anti-cancer agents, delayed the tumor growth and prolonged the mice survival in a range of 45% -70%. It appears that the targeted liposomal drug-delivery system enables better therapeutic efficacy in a SCID mouse model of glioblastoma compared to the corresponding non-targeted liposomes and the free compounds. Keywords APP-targeted liposomes · Glioblastoma · Blood–brain barrier (BBB) · Temozolomide (TMZ) · Curcumin · Doxorubicin
Introduction The blood–brain barrier (BBB) is a continuous endothelial membrane that along with components of the neurovascular unit of pericytes and astrocytes, limits the entry of toxins, Nahum Allon—Deceased during the development of this study. * Moshe Gavish [email protected] 1
The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, 31096 Haifa, Israel
2
Research Unit, Geha Mental Health Center and the Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, 4910002 Petah Tikva, Israel
3
Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel
pathogens, and cells into the brain (Zlokovic, 2011). Due to the unique structure of this barrier that includes a monolayer of polarized endothelial cells in
Data Loading...
