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A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Dipsacus Asperoides-Derived Exosomes-Like Nanoparticles Inhibit the Progression of Osteosarcoma via Activating
Jiaxu Lu1,2, Jiaxian Chen2, Junhong Ye2
1Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People's Republic of China.
Introduction:
Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo.
Methods:
DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry.
Results:
Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis.
Conclusion:
Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.
Insights
Exosome-like nanoparticles from Dipsacus asperoides (DAELNs) show potent anti-osteosarcoma effects by inducing apoptosis via the P38/JNK pathway. These natural agents offer a promising, safer alternative for osteosarcoma treatment.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Oncology
Background:
- Osteosarcoma is a highly malignant bone tumor with limited long-term therapeutic options due to severe side effects.
- Traditional Chinese medicine offers potential for developing novel anti-cancer agents with improved safety profiles.
Purpose of the Study:
- To investigate the therapeutic potential of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) against osteosarcoma.
- To elucidate the underlying mechanism of DAELNs in inhibiting osteosarcoma progression.
Main Methods:
- Isolation and characterization of DAELNs using TEM and NTA.
- In vitro assessment of DAELN effects on osteosarcoma cell proliferation, invasion, migration, and apoptosis.
- In vivo evaluation of DAELN efficacy and biodistribution in a xenograft mouse model.
- Investigation of the P38/JNK signaling pathway activation by DAELNs.
Main Results:
- DAELNs significantly inhibited osteosarcoma cell proliferation, invasion, and migration while promoting apoptosis in vitro.
- DAELNs suppressed tumor growth in a xenograft nude mouse model.
- DiD-labeled DAELNs demonstrated preferential tumor targeting and good biosafety in major organs.
- DAELNs were found to activate the P38/JNK signaling pathway, leading to apoptosis.
Conclusions:
- DAELNs represent novel, natural, and targeted therapeutic agents for osteosarcoma.
- DAELNs exhibit significant anti-tumor efficacy and favorable biosafety, suggesting their potential as a safe and effective treatment for osteosarcoma.
