title: Cationic lipid-assisted polymeric nanoparticle mediated GATA2 siRNA delivery for synthetic lethal therapy of KRAS mutant non-small-cell lung carcinoma.
abstract: Synthetic lethal interaction provides a conceptual framework for the development of wiser cancer therapeutics. In this study, we exploited a therapeutic strategy based on the interaction between GATA binding protein 2 (GATA2) downregulation and the KRAS mutation status by delivering small interfering RNA targeting GATA2 (siGATA2) with cationic lipid-assisted polymeric nanoparticles for treatment of non-small-cell lung carcinoma (NSCLC) harboring oncogenic KRAS mutations. Nanoparticles carrying siGATA2 (NPsiGATA2) were effectively taken up by NSCLC cells and resulted in targeted gene suppression. NPsiGATA2 selectively inhibited cell proliferation and induced cell apoptosis in KRAS mutant NSCLC cells. However, this intervention was harmless to normal KRAS wild-type NSCLC cells and HL7702 hepatocytes, confirming the advantage of synthetic lethality-based therapy. Moreover, systemic delivery of NPsiGATA2 significantly inhibited tumor growth in the KRAS mutant A549 NSCLC xenograft murine model, suggesting the therapeutic promise of NPsiGATA2 delivery in KRAS mutant NSCLC therapy.
authors: School of Life Sciences and ‡Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, Anhui 230027, P. R. China.
authors: Song
authors: S
authors: Shen
authors: Chong-Qiong
authors: CQ
authors: Mao
authors: Xian-Zhu
authors: XZ
authors: Yang
authors: Xiao-Jiao
authors: XJ
authors: Du
authors: Yang
authors: Y
authors: Liu
authors: Yan-Hua
authors: YH
authors: Zhu
authors: Jun
authors: J
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002412:Cations; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050989:GATA2 Transcription Factor / Q000378:metabolism* / Q000627:therapeutic use; D020868:Gene Silencing; D011905:Genes, ras; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009154:Mutation; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002412:Cations; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D011108:Polymers; D034741:RNA, Small Interfering