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

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.

Keywords:

• K-RAS
• lung cancer
• metabolomic
• poly (D
• L-lactic-co-glycolic acid)
• polymeric nanoparticle
• siRNA

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests.

Additional information

Funding

This work was supported by the Scientifıc and Technological Research Council of Turkey (TUBİTAK) (Grant number: 1001-118S452). Ayse Gencer is supported by The Scientifıc and Technological Research Council of Turkey (grant number: TUBİTAK 2211-A).