Inhibition of osteosarcoma growth and metastasis using a polysaccharide derivative of Amy-g-PLLD for the delivery of AEG-1 siRNA
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Osteosarcoma is the most common primary malignant neoplasm of the bone in children and adolescents and has a high risk of relapse and metastasis. Of the various methods to treat osteosarcoma, the use of genetic approaches to inhibit the rapid growth of osteosarcoma while limiting tumor metastasis has presented a challenge in its implementation. Here, we successfully synthesized a polysaccharide derivative (Amy-g-PLLD) for delivery of astrocyte elevated gene-1 (AEG-1) small-interfering RNA (siRNA) (siAEG-1), and used it for the first time to suppress osteosarcoma tumors in vitro and in vivo. Amy-g-PLLD/ siAEG-1 complexes were delivered into 143B human osteosarcoma cells with low resultant cytotoxicity. Osteosarcoma tumor proliferation and invasion were inhibited in vitro. Intratumoral injection of Amy-g-PLLD/siAEG-1 complexes markedly inhibited tumor growth and lung metastasis in 143B tumor-bearing mice. This biocompatible and effective approach employing a natural material-siRNA complex should pave the way for more genetic research in treating osteosarcoma.
Keywordsosteosarcoma amylose gene delivery astrocyte elevated gene-1 (AEG-1) small-interfering RNA (siRNA)
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This work was supported by the National Natural Science Foundation of China (Nos. 81402221 and 51273216), the Research Fund for the Doctoral Program of Higher Education of China (No. 20130171120077), the Science and Technology Program of Guangzhou, China (No. 201707010108), the Guangdong Innovative Research Team Program (No. 2009010057), and the Science and Technology Planning Project of Guangzhou (No. 201610010006), the Science and Technology Planning project of Guangdong Province (No. 20153900042020319) and Natural Science Foundation of Guangdong Province (No. 2016A030313819).
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