In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer

Int J Pharm. 2017 Jun 20;525(2):377-387. doi: 10.1016/j.ijpharm.2017.02.020. Epub 2017 Feb 9.


Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour. siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.

Keywords: 3-sn-Phosphatidylcholine (PubChem CID: 16213884); Cholesterol (PubChem CID: 5997); Colonic mucosa; Colorectal cancer; DOTAP- N-[1-(2,3-Dioleoyloxy)Propyl]-N,N,N-trimethylammonium Chloride (PubChem CID: 123922); E2F1; MTT -3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (PubChem CID: 64966); Nanoliposome; siRNA delivery.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / therapy
  • E2F1 Transcription Factor / genetics*
  • Gene Silencing*
  • Humans
  • Liposomes / chemistry
  • Nanoparticles / chemistry
  • RNA, Small Interfering / administration & dosage*
  • Transfection
  • Ultrasonography


  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Liposomes
  • RNA, Small Interfering