Chitosan Nanoparticles Loaded with TGF- β 1 Inhibit Cervical Cancer Cell Progression Through Down-Regulation of MicroRNA-155 and Activation of Tim-3 Pathway

J Biomed Nanotechnol. 2021 Sep 1;17(9):1850-1857. doi: 10.1166/jbn.2021.3146.


Chemically modified chitosan nanoparticles (NPs) are capable of releasing their own substances to target cells or tissues, improving microenvironment and promoting wound healing. This study aimed to explore the molecular mechanism underlying chitosan NPs loaded with TGF-β1 participating in cervical cancer (CC) progression. TGF-β1-loaded-chitosan NPs were prepared and particle size distribution, zeta potential and encapsulation efficiency of NPs were determined. MTT assay assessed the toxicity of NPs to macrophages. CC cells were co-cultured with TGF-β1-loaded chitosan NPs (experimental group) or pure chitosan NPs (control group) and cells were cultured alone to produce control group. After treatment, flow cytometry was conducted to detect apoptosis and cycle. Cancer cell migration was evaluated by Transwell assay, and miR-155 and Tim-3 expression was determined. At a ratio of 2:1 chitosan and TGF-β1, the particle size was102.65±11.98 nm, which was smallest, with high encapsulation rate of 81.26%, and low potential of 1.46±1.71. NP toxicity increased as concentration rose and relative cell proliferation rate was >80%, indicated as non-toxic. CC tissues had positive expression of CD163 and TGF-β1 (95%) (p < 0.05). Treatment with TGF-β1-loaded chitosan NPs induced increased apoptosis rate of 9.13±2.15%, reduced migration (67.65±9.91) and invaded cells (19.98±3.41), causing cell accumulation in the S phase when compared to the blank and control groups (p < 0.05). Besides, experimental group exhibited lower expression of miR-155 (0.39±0.59) and higher expression of Tim-3 (2.87± 0.51), which was higher than the blank group and control group. The optimal concentration ratio for producing TGF-β1-loaded chitosan NPs was 2:1, with less toxicity. The composite NPs suppressed malignant characteristics of CC cells through down-regulation of miR-155 and activation of Tim-3 signal pathway on the surface of macrophages, promoting secretion of macrophage inflammatory factors.

MeSH terms

  • Chitosan*
  • Down-Regulation
  • Female
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • MicroRNAs* / genetics
  • Nanoparticles*
  • Transforming Growth Factor beta1 / genetics
  • Tumor Microenvironment
  • Uterine Cervical Neoplasms* / drug therapy


  • Hepatitis A Virus Cellular Receptor 2
  • MIRN155 microRNA, human
  • MicroRNAs
  • Transforming Growth Factor beta1
  • Chitosan