Theranostics 2018; 8(5):1361-1375. doi:10.7150/thno.18299 This issue Cite

Research Paper

Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis

Suoyuan Li1,4*, Tao Zhang1*, Weiguo Xu2*, Jianxun Ding2✉, Fei Yin3, Jing Xu3, Wei Sun1, Hongsheng Wang3, Mengxiong Sun1, Zhengdong Cai1,3✉, Yingqi Hua1,3✉

1. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P. R. China
2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
3. Shanghai Bone Tumor Institution, Shanghai 201620, P. R. China
4. Department of Orthopedics, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou 215000, P. R. China
*These authors contributed equally to this work.

Citation:
Li S, Zhang T, Xu W, Ding J, Yin F, Xu J, Sun W, Wang H, Sun M, Cai Z, Hua Y. Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis. Theranostics 2018; 8(5):1361-1375. doi:10.7150/thno.18299. https://www.thno.org/v08p1361.htm
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Abstract

Graphic abstract

Purpose: Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed.

Design: In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity.

Results: The targeted, loaded nanogel, STP-NG/SHK, killed osteosarcoma cells by inducing RIP1- and RIP3-dependent necroptosis in vitro. Necroptosis is a novel cell death form that could be well adapted as an efficient antitumor strategy, the main obstacle of which is its high toxicity. After intravenous injection, STP-NG/SHK efficiently suppressed tumor growth and reduced pulmonary metastasis, offering greater tumor necrosis and higher RIP1 and RIP3 upregulation compared to free SHK or untargeted NG/SHK in vivo. Additionally, the treatment with NG/SHK or STP-NG/SHK showed minimal toxicity to normal organs, suggesting low systemic toxicity compared to free SHK. Conclusion: The STP-guided intracellular drug delivery system using the necroptosis mechanism showed profound anti-osteosarcoma activity, especially eliminated lung metastasis in vivo. This drug formulation may have great potential for treatment of osteosarcoma.

Keywords: Sarcoma-Targeting Peptide, Polypeptide Nanogel, Intracellular Drug Delivery, Necroptosis, Osteosarcoma Chemotherapy


Citation styles

APA
Li, S., Zhang, T., Xu, W., Ding, J., Yin, F., Xu, J., Sun, W., Wang, H., Sun, M., Cai, Z., Hua, Y. (2018). Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis. Theranostics, 8(5), 1361-1375. https://doi.org/10.7150/thno.18299.

ACS
Li, S.; Zhang, T.; Xu, W.; Ding, J.; Yin, F.; Xu, J.; Sun, W.; Wang, H.; Sun, M.; Cai, Z.; Hua, Y. Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis. Theranostics 2018, 8 (5), 1361-1375. DOI: 10.7150/thno.18299.

NLM
Li S, Zhang T, Xu W, Ding J, Yin F, Xu J, Sun W, Wang H, Sun M, Cai Z, Hua Y. Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis. Theranostics 2018; 8(5):1361-1375. doi:10.7150/thno.18299. https://www.thno.org/v08p1361.htm

CSE
Li S, Zhang T, Xu W, Ding J, Yin F, Xu J, Sun W, Wang H, Sun M, Cai Z, Hua Y. 2018. Sarcoma-Targeting Peptide-Decorated Polypeptide Nanogel Intracellularly Delivers Shikonin for Upregulated Osteosarcoma Necroptosis and Diminished Pulmonary Metastasis. Theranostics. 8(5):1361-1375.

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