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Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for

Jun-Yi Wu1, Zhong-Xia Wang1, Guang Zhang1

  • 1Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

International Journal of Nanomedicine
|March 20, 2018
PubMed
Abstract

Insights

This study developed calcium phosphate nanoparticles for co-delivery of fingolimod (FTY720) and Beclin 1 siRNA to enhance hepatocellular carcinoma (HCC) treatment. The combined therapy significantly boosted anticancer effects both in vitro and in vivo.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Fingolimod (FTY720) exhibits anticancer properties but can induce protective autophagy, limiting its efficacy.
  • Blocking autophagy with Beclin 1 siRNA enhances apoptosis, suggesting a synergistic therapeutic strategy.
  • Hepatocellular carcinoma (HCC) remains a significant health challenge requiring novel treatment approaches.

Purpose of the Study:

  • To enhance the anticancer effect of FTY720 in HCC by co-delivering it with Beclin 1 siRNA.
  • To utilize calcium phosphate (CaP) nanoparticles (NPs) for targeted delivery of FTY720 and Beclin 1 siRNA.
  • To investigate the efficacy of this combined therapeutic strategy in HCC models.

Main Methods:

  • siRNA was encapsulated in CaP NPs with an asymmetric lipid bilayer containing FTY720.
  • Nanoparticle characterization included TEM, DLS, and UV-Vis spectrophotometry.
  • In vitro and in vivo anticancer efficacy was assessed using cell viability assays, flow cytometry, Western blotting, and a mouse tumor model.

Main Results:

  • The developed CaP NPs (LCP-II NPs) successfully co-delivered FTY720 and Beclin 1 siRNA, showing appropriate size and cellular uptake.
  • The NPs demonstrated stability in systemic circulation.
  • Co-delivery significantly enhanced cytotoxicity in vitro and tumor suppression in vivo compared to FTY720 alone.

Conclusions:

  • The CaP NP system is a promising platform for co-delivering FTY720 and Beclin 1 siRNA to improve HCC treatment outcomes.
  • This approach offers a novel strategy for HCC therapy by combining small molecules and siRNA delivery.
  • The findings have potential for translation into clinical trials for cancer treatment.
Keywords:
Beclin 1FTY720LCP-II NPsautophagyco-delivery

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