期刊
MOLECULAR PHARMACEUTICS
卷 14, 期 9, 页码 3218-3227出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00519
关键词
tethered lipid bilayers; mesoporous silica nanoparticles; zoledronic acid; breast cancer
资金
- Academy of Finland [260599, 284542]
- Finnish Cultural Foundation
- Cancer Society of Finland
- Basic Advanced Research Project of Chongqing [cstc2015jcyjA10051]
- Jane and Aatos Erkko Foundation
- Cancer Society of South-West Finland
- K. Albin Johansson foundation
- Turku University Foundation
- BGG graduate school of the University of Turku
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.
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