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

被引:5
|
作者
Gencer, Ayse [1 ]
Baysal, Ipek [2 ]
Nemutlu, Emirhan [3 ]
Yabanoglu-Ciftci, Samiye [4 ]
Arica, Betul [1 ]
机构
[1] Hacettepe Univ, Dept Pharmaceut Technol, Fac Pharm, Ankara, Turkey
[2] Hacettepe Univ, Vocat Sch Hlth Serv, Ankara, Turkey
[3] Hacettepe Univ, Dept Analyt Chem, Fac Pharm, Ankara, Turkey
[4] Hacettepe Univ, Dept Biochem, Fac Pharm, Ankara, Turkey
关键词
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;
D O I
10.1080/02652048.2022.2061058
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
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.
引用
收藏
页码:261 / 275
页数:15
相关论文
共 50 条
  • [21] DNA damage, superoxide, and mutant K-ras in human lung adenocarcinoma cells
    Romanowska, Malgorzata
    Maciag, Anna
    Smith, Andrew L.
    Fields, Janet R.
    Fornwald, Laura W.
    Kikawa, Keith D.
    Kasprzak, Kazimierz S.
    Anderson, Lucy M.
    FREE RADICAL BIOLOGY AND MEDICINE, 2007, 43 (08) : 1145 - 1155
  • [22] Akt1 deletion prevents lung tumorigenesis by mutant K-ras
    M C Hollander
    C R Maier
    E A Hobbs
    A R Ashmore
    R I Linnoila
    P A Dennis
    Oncogene, 2011, 30 : 1812 - 1821
  • [23] K-Ras role in lung cancer therapy
    Zhang, Z.
    Wang, Zhou
    MINERVA CHIRURGICA, 2011, 66 (03) : 251 - 268
  • [24] K-ras point mutation occurs in the early stage of carcinogenesis in lung cancer
    Sagawa, M
    Saito, Y
    Fujimura, S
    Linnoila, RI
    BRITISH JOURNAL OF CANCER, 1998, 77 (05) : 720 - 723
  • [25] A simple look at the molecular biology of lung cancer: K-Ras
    Lena, H.
    Corre, R.
    Denis, M.
    REVUE DES MALADIES RESPIRATOIRES, 2010, 27 (06) : 639 - 643
  • [26] Akt1 deletion prevents lung tumorigenesis by mutant K-ras
    Hollander, M. C.
    Maier, C. R.
    Hobbs, E. A.
    Ashmore, A. R.
    Linnoila, R. I.
    Dennis, P. A.
    ONCOGENE, 2011, 30 (15) : 1812 - 1821
  • [27] Biodegradable Nanocapsules as siRNA Carriers for Mutant K-Ras Gene Silencing of Human Pancreatic Carcinoma Cells
    Lin, Guimiao
    Hu, Rui
    Law, Wing-Cheung
    Chen, Chih-Kuang
    Wang, Yucheng
    Chin, Hui Li
    Quoc Toan Nguyen
    Lai, Cheng Kee
    Yoon, Ho Sup
    Wang, Xiaomei
    Xu, Gaixia
    Ye, Ling
    Cheng, Chong
    Yong, Ken-Tye
    SMALL, 2013, 9 (16) : 2757 - 2763
  • [28] Study of SiRNA-loaded PS-mPEG/CaP nanospheres on lung cancer
    Qi Wang
    Liubin Qin
    Ying Sun
    Ming Shen
    Yourong Duan
    Journal of Nanoparticle Research, 2014, 16
  • [29] Study of SiRNA-loaded PS-mPEG/CaP nanospheres on lung cancer
    Wang, Qi
    Qin, Liubin
    Sun, Ying
    Shen, Ming
    Duan, Yourong
    JOURNAL OF NANOPARTICLE RESEARCH, 2014, 16 (05)
  • [30] Comparative Evaluation of siRNA-loaded Chitosan Tripolyphosphate/Dextran Sulfate Nanoparticles Prepared by Adsorption Method: In Vitro Characterizations
    Raja, Maria Abdul Ghafoor
    Amjad, Muhammad Wahab
    Hassan, Khidir A. M.
    INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND PHYTOPHARMACOLOGICAL RESEARCH, 2018, 8 (05): : 1 - 6