Efficacy of siRNA-loaded nanoparticles in the treatment of K-RAS mutant lung cancer in vitro

Gencer A., BAYSAL İ., NEMUTLU E., YABANOĞLU ÇİFTÇİ S., ARICA YEGİN B.

JOURNAL OF MICROENCAPSULATION, vol.39, no.3, pp.261-275, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1080/02652048.2022.2061058
  • Journal Name: JOURNAL OF MICROENCAPSULATION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.261-275
  • Keywords: K-RAS, lung cancer, metabolomic, poly (D, L-lactic-co-glycolic acid), polymeric nanoparticle, siRNA, DRUG-DELIVERY, GENE DELIVERY, POLYMERIC NANOPARTICLES, CHITOSAN NANOPARTICLES, PLGA NANOPARTICLES, RNA INTERFERENCE, KRAS, THERAPY, FORMULATION, METABOLISM
  • Hacettepe University Affiliated: Yes

Abstract

To design and develop K-RAS silencing small interfering RNA (siRNA)-loaded poly (D, L-lactic-co-glycolic acid) nanoparticles and evaluate their efficacy in the treatment of K-RAS mutant lung cancer. The nanoparticles prepared by the double emulsion solvent evaporation method were characterized by TEM, FTIR and XPS analyzes and evaluated in vitro by XTT, PCR, ELISA, and Western-Blot. Metabolomic analyzes were performed to evaluate the changes in metabolic profiles of the cells after nanoparticles treatment. The nanoparticles were obtained with a particle size less than 250 nm, a polydispersity index around 0.1, a surface charge of (-12) - (+14) mV, and 80% of the siRNA encapsulation. The nanoparticles didn't affect cell viability of the cells after 72 hours. In cancer cells, KRAS expression was decreased by up to 50%, protein levels were decreased by more than 90%. The formulated siRNA delivery nanoparticles can be promising treatment in lung cancer.