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Zoledronic Acid-Loaded β-TCP Inhibits Tumor Proliferation and Osteoclast Activation: Development of a Functional Bone Substitute for an Efficient Osteosarcoma Treatment.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Feb 14; Vol. 22 (4). Date of Electronic Publication: 2021 Feb 14. - Publication Year :
- 2021
-
Abstract
- Osteosarcoma has a poor survival rate due to relapse and metastasis. Zoledronic acid (ZOL), an anti-resorptive and anti-tumor agent, is used for treating osteosarcoma. Delivery of ZOL to the target region is difficult due to its high binding affinity to bone minerals. This study developed a novel treatment for osteosarcoma by delivering ZOL to the target region locally and sustainably. In this study, we fabricated a novel bone substitute by loading ZOL on β-tricalcium phosphate (β-TCP). The ZOL-loaded β-TCP (ZOL/β-TCP) would be expected to express the inhibitory effects via both bound-ZOL (bound to β-TCP) and free-ZOL (release from ZOL/β-TCP). To explore the ability to release ZOL from the ZOL/β-TCP, the amount of released ZOL was measured. The released profile indicates that a small amount of ZOL was released, and most of it remained on the β-TCP. Our data showed that ZOL/β-TCP could successfully express the effects of ZOL via both bound-ZOL and free-ZOL. In addition, we examined the biological effects of bound/free-ZOL using osteosarcoma and osteoclasts (target cells). The results showed that two states of ZOL (bound/free) inhibit target cell activities. As a result, ZOL/β-TCP is a promising candidate for application as a novel bone substitute.
- Subjects :
- Animals
Bone Substitutes chemistry
Bone Substitutes pharmacokinetics
Bone Substitutes pharmacology
Calcium Phosphates chemistry
Calcium Phosphates pharmacokinetics
Cell Differentiation drug effects
Cell Line
Cell Line, Tumor
Cell Survival drug effects
Cells, Cultured
Culture Media, Conditioned pharmacology
Drug Liberation
Humans
Male
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells metabolism
Mice, Inbred C57BL
Osteosarcoma pathology
Zoledronic Acid chemistry
Zoledronic Acid pharmacokinetics
Mice
Calcium Phosphates pharmacology
Cell Proliferation drug effects
Osteoclasts metabolism
Osteosarcoma metabolism
Zoledronic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33672879
- Full Text :
- https://doi.org/10.3390/ijms22041889