2. Academic Validation
  3. Protective effect of melatonin entrapped PLGA nanoparticles on radiation-induced lung injury through the miR-21/TGF-β1/Smad3 pathway

Protective effect of melatonin entrapped PLGA nanoparticles on radiation-induced lung injury through the miR-21/TGF-β1/Smad3 pathway

  • Int J Pharm. 2021 Jun 1;602:120584. doi: 10.1016/j.ijpharm.2021.120584.
Shuang Wang 1,  Juan Li 1,  Yingjuan He 1,  Yonghong Ran 1,  Binghui Lu 1,  Jining Gao 1,  Chang Shu 1,  Jie Li 1,  Yazhen Zhao 1,  Xin Zhang 2,  Yuhui Hao 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No.30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
  • 2 Chongqing Normal University, No.37, Middle University Road, Shapingba District, Chongqing 401331, China.
  • 3 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No.30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: [email protected].
PMID: 33887395 DOI: 10.1016/j.ijpharm.2021.120584
Abstract

Radiation-induced lung injury (RILI) is a complication commonly found in victims suffering from nuclear accidents and patients treated with chest tumor radiotherapy, and drugs are limited for effective prevention and treatment. Melatonin (MET) has an anti-radiation effect, but its metabolic period in the body is short. In order to prolong the metabolism period of MET, we prepared MET entrapped poly (lactic-co-glycolic acid) nanoparticles (MET/PLGANPS) for the treatment of RILI. As a result, the release rate of MET/PLGANPS in vitro was lower than MET, with stable physical properties, and it caused no changes in histopathology and biochemical indicators. After 2 weeks and 16 weeks of irradiation with the dose of 15 Gy, MET and MET/PLGANPS could reduce the expression of Caspase-3 proteins, inflammatory factors, TGF-β1 and SMAD3 to alleviate radiation-induced lung injury. MET/PLGANPS showed better therapeutic effect on RILI than MET. In addition, we also found that high expression of miR-21 could increase the expression levels of TGF-β1, and inhibit the protective effect of MET/PLGANPS. In conclusion, MET/PLGANPS may alleviate RILI by inhibiting the miR-21/TGF-β1/SMAD3 pathway, which would provide a new target for the treatment of radiation-induced lung injury.

Keywords

Melatonin; Nanoparticles; Radiation-induced lung injury; Smad3; TGF-β1; miR-21.

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