Lipid Bilayer-Gated Mesoporous Silica Nanocarriers for Tumor-Targeted Delivery of Zoledronic Acid in Vivo
Autor: | Diti Desai, Jaakko Lehtimäki, Tove J. Grönroos, Jouko Sandholm, Johanna Tuomela, Jixi Zhang, Jessica M. Rosenholm |
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Rok vydání: | 2017 |
Předmět: |
medicine.medical_treatment
ta221 Lipid Bilayers Mice Nude Pharmaceutical Science 02 engineering and technology Pharmacology ta3111 Zoledronic Acid Mice 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor Drug Discovery medicine Animals Humans Viability assay ta216 Lipid bilayer ta215 Diphosphonates Chemistry ta1182 Imidazoles Mesoporous silica Bisphosphonate ta3122 Flow Cytometry Silicon Dioxide 021001 nanoscience & nanotechnology Immunohistochemistry In vitro Zoledronic acid 030220 oncology & carcinogenesis Nanoparticles Molecular Medicine Nanocarriers 0210 nano-technology Porosity medicine.drug |
Zdroj: | Molecular Pharmaceutics. 14:3218-3227 |
ISSN: | 1543-8392 1543-8384 |
Popis: | Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate used for the treatment of bone diseases and calcium metabolism. Anticancer activity of ZOL has been established, but its extraskeletal effects are limited due to its rapid uptake and accumulation to bone hydroxyapatite. In this work, we report on the development of tethered lipid bilayer-gated mesoporous silica nanocarriers (MSNs) for the incorporation, retention, and intracellular delivery of ZOL. The in vitro anticancer activity of ZOL-loaded nanocarriers was evaluated by cell viability assay and live-cell imaging. For in vivo delivery, the nanocarriers were tagged with folic acid to boost the affinity for breast cancer cells. Histological examination of the liver revealed no adverse off-target effects stemming from the nanocarriers. Importantly, nonspecific accumulation of ZOL within bone was not observed, which indicated in vivo stability of the tethered lipid bilayers. Further, the intravenously administered ZOL-loaded nanocarriers showed tumor growth suppression in breast cancer xenograft-bearing mice. |
Databáze: | OpenAIRE |
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