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Updated: Sep 5, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Identification of Small-Molecule Inhibitors for Osteosarcoma Targeted Therapy: Synchronizing In Silico, In Vitro, and
1School of Basic Medical Sciences, Affiliated Hospital, School of Mechanical Engineering, Chengdu University, Chengdu, China.
Abstract:
Objective: The study aimed to explore a new approach for the treatment of osteosarcoma through combining biomaterials with next-generation small molecule-based targeted therapy. Methods: The model of osteosarcoma was established by 4-hydroxyaminoquinoline 1-oxide (4-HAQO) in mice while the collagen-thermosensitive hydrogel-calcium phosphate (CTC) biocomposites were prepared, and the small molecule inhibitors were virtually screened and synthesized. Then, for the osteosarcoma cell line, MG-63 cells were used to validate our bioinformatic findings in vitro, and the mouse osteosarcoma models were treated by combing CTC composites and small-molecule inhibitors after debridement. Results: Five compounds, namely, ZINC150338698, ZINC14768621, ZINC4217203, ZINC169291448, and ZINC85537017, were found in the ZINK database. Finally, ZINC150338698 was selected for chemical synthesis and experimental verification. The results of the MTT assay and Hoechst staining showed that the small-molecule inhibitor ZINC150338698 could significantly induce MG-63 cell death. Furthermore, CTC composites and ZINC150338698 could repair the bone defects well after the debridement of osteosarcoma. In addition, the biomaterials and small-molecule inhibitors have good biocompatibility and biosafety. Conclusion: Our findings not only offer systems biology approach-based drug target identification but also provide new clues for developing novel treatment methods for future osteosarcoma research.
Insights
This study introduces a novel osteosarcoma treatment combining biomaterials with targeted small molecule therapy. The developed collagen-thermosensitive hydrogel-calcium phosphate (CTC) biocomposites and ZINC150338698 inhibitor effectively treated osteosarcoma in mice.
Area of Science:
- Biomaterials Science
- Oncology
- Pharmacology
Background:
- Osteosarcoma presents a significant challenge in orthopedic oncology.
- Targeted therapies offer potential for improved treatment efficacy and reduced toxicity.
- Biomaterial scaffolds can enhance drug delivery and tissue regeneration.
Purpose of the Study:
- To develop a novel therapeutic strategy for osteosarcoma by integrating biomaterials with small molecule targeted therapy.
- To identify and synthesize effective small molecule inhibitors for osteosarcoma treatment.
- To evaluate the efficacy and safety of combined biomaterial and targeted therapy in preclinical models.
Main Methods:
- Osteosarcoma mouse models were established using 4-hydroxyaminoquinoline 1-oxide (4-HAQO).
- Collagen-thermosensitive hydrogel-calcium phosphate (CTC) biocomposites were prepared.
- Small molecule inhibitors were identified via virtual screening and synthesized, with ZINC150338698 selected for validation.
- In vitro studies used MG-63 cells, followed by in vivo treatment of mouse models with CTC composites and ZINC150338698 post-debridement.
Main Results:
- Virtual screening identified five potential compounds, with ZINC150338698 selected for synthesis and testing.
- MTT assays and Hoechst staining confirmed ZINC150338698 significantly induced MG-63 cell death.
- Combined CTC composites and ZINC150338698 demonstrated effective repair of bone defects in osteosarcoma models.
- The developed biomaterials and small-molecule inhibitor exhibited good biocompatibility and biosafety.
Conclusions:
- This study presents a systems biology approach for identifying drug targets in osteosarcoma.
- The combination of CTC biocomposites and ZINC150338698 offers a promising new therapeutic avenue for osteosarcoma.
- Findings provide novel insights for future research and development of osteosarcoma treatments.
