E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cells

Autor: Gholizadeh Soltani, Shima, Visweswaran, Ganesh Ram R, Storm, G, Hennink, Wim E., Kamps, Jan A A M, Kok, Robbert J., Afd Pharmaceutics, Pharmaceutics
Přispěvatelé: Afd Pharmaceutics, Pharmaceutics, Nanotechnology and Biophysics in Medicine (NANOBIOMED)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
CANCER-THERAPY
EXPERIMENTAL ARTHRITIS
Cell Survival
media_common.quotation_subject
Endothelial cells
Pharmaceutical Science
02 engineering and technology
Mice
03 medical and health sciences
Drug Delivery Systems
E-selectin
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Rapamycin
Internalization
LIPID-BILAYERS
Protein kinase B
PI3K/AKT/mTOR pathway
media_common
Sirolimus
Dose-Response Relationship
Drug
biology
Immunoliposomes
MTOR
technology
industry
and agriculture
ACTIN CYTOSKELETON
IN-VITRO
021001 nanoscience & nanotechnology
Actin cytoskeleton
Molecular biology
TNF-ALPHA
In vitro
Anti-Bacterial Agents
PROTEIN-KINASE B
RHEUMATOID-ARTHRITIS
030104 developmental biology
MAMMALIAN TARGET
Liposomes
biology.protein
Cancer research
Tumor necrosis factor alpha
Targeted delivery
E-Selectin
0210 nano-technology
medicine.drug
Zdroj: International Journal of Pharmaceutics, 548(2), 759. Elsevier bedrijfsinformatie b.v.
International Journal of Pharmaceutics, 548(2), 759-770. Elsevier Bedrijfsinformatie b.v.
ISSN: 0378-5173
Popis: Activated endothelial cells play a pivotal role in the pathology of inflammatory disorders and thus present a target for therapeutic intervention by drugs that intervene in inflammatory signaling cascades, such as rapamycin (mammalian target of rapamycin (mTOR) inhibitor). In this study we developed anti-E-selectin immunoliposomes for targeted delivery to E-selectin over-expressing tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3.; hosphocholine (DPPC), Cholesterol, and 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleimide (DSPE-PEG- Mal) were loaded with rapamycin via lipid film hydration, after which they were further functionalized by coupling N-succinimidyl-S-acetylthioacetate (SATA)-modified mouse anti human E-selectin antibodies to the distal ends of the maleimidyl (Mal)-PEG groups. In cell binding assays, these immunoliposomes bound specifically to TNF-alpha activated endothelial cells. Upon internalization, rapamycin loaded immunoliposomes inhibited proliferation and migration of endothelial cells, as well as expression of inflammatory mediators. Our findings demonstrate that rapamycin-loaded immunoliposomes can specifically inhibit inflammatory responses in inflamed endothelial cells.
Databáze: OpenAIRE
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