Magnetically responsive nanoplatform targeting circRNA circ_0058051 inhibits hepatocellular carcinoma progression

Drug Deliv Transl Res. 2023 Mar;13(3):782-794. doi: 10.1007/s13346-022-01237-z. Epub 2022 Sep 16.

Abstract

Circular RNAs (circRNAs) are a class of highly stable and closed-loop noncoding RNA that are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 knockdown attenuated the proliferation and colony formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system, PEG-PCL-PEI-C14-SPIONs (PPPCSs), based on superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected the siRNA of circ_0058051 from degradation in serum and effectively delivered siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment.

Keywords: HCC; SPIONs; circ_0058051; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Liver Neoplasms* / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • RNA, Small Interfering / genetics

Substances

  • RNA, Circular
  • MicroRNAs
  • RNA, Small Interfering