Lipid Bilayer-Gated Mesoporous Silica Nanocarriers for Tumor-Targeted Delivery of Zoledronic Acid in Vivo.

Abstract

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.

• Authors: Diti Desai, Jixi Zhang, Jouko Sandholm, Jaakko Lehtimäki, Tove Grönroos, Johanna Tuomela, Jessica M Rosenholm
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 14 Issue 9 Pg. 3218-3227 (09 05 2017) ISSN: 1543-8392 [Electronic] United States
• PMID: 28737925 (Publication Type: Journal Article)

Chemical References

• Diphosphonates
• Imidazoles
• Lipid Bilayers
• Zoledronic Acid
• Silicon Dioxide

Topics

• Animals
• Cell Line, Tumor
• Diphosphonates (administration & dosage, chemistry)
• Flow Cytometry
• Humans
• Imidazoles (administration & dosage, chemistry)
• Immunohistochemistry
• Lipid Bilayers (chemistry)
• Mice
• Mice, Nude
• Nanoparticles (chemistry)
• Porosity
• Silicon Dioxide (chemistry)
• Zoledronic Acid