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  2. 3D-printing magnesium-polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures

3D-printing magnesium-polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures

  • J Nanobiotechnology. 2021 Sep 4;19(1):263. doi: 10.1186/s12951-021-01012-1.
Weilin Zhang  # 1 Wei Zhao  # 1 Qin Li 2 Duoyi Zhao 1 Junxing Qu 1 Ziyang Yuan 1 Zhihong Cheng 1 Xiaojuan Zhu 3 Xiuli Zhuang 4 Zhiyu Zhang 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, Liaoning, China.
  • 2 Translational Medicine Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
  • 3 Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun, Jilin, China.
  • 4 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun, Jilin, China.
  • 5 Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, Liaoning, China. zyzhang@cmu.edu.cn.
  • # Contributed equally.
Abstract

Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium-polycaprolactone (Mg-PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg-PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg-PCL scaffold as well as melatonin-loaded Mg-PCL on OS growth and progression were investigated in vivo and in vitro. We found that Melatonin Receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg-PCL-MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg-PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg-PCL-MT could be a potential therapeutics for OS.

Keywords

Cell-in-cell; Melatonin; Mg–PCL; Osteosarcoma; Rho/ROCK; cAMP/PKA signaling pathway.

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