Skip to content
2000
Volume 22, Issue 7
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Liver cancer is the sixth most common cancer and the fourth leading cause of death worldwide. Hepatocellular carcinoma (HCC) comprises 75-80% of liver cancer cases. Therapeutic strategies for HCC are available and have been shown to prolong survival but do not treat HCC. Gene expression and regulation are responsible for the pathogenesis and progression of HCC. Altering these genetic networks can impact cellular behaviors and in turn cure HCC. Single-stranded and double-stranded non-coding ribonucleic acid known as microRNA and small interfering RNA, respectively have been investigated as possible therapeutic options. Currently, efficient delivery systems that ensure cell-specific targeting and efficient transfection into tumor cells are still under investigation. Viral vectors have been studied extensively, but immunogenicity hinders their use as delivery systems. Non-viral vectors which include inorganic, lipid, or polymeric nanoparticles are promising delivery systems. However, there are a lot of challenges during the formulation of such systems to ensure efficient and specific delivery. and studies have investigated different lipid nanoparticles (LNPs) to deliver miRNA or siRNA. In this review, we highlight the role of LNPs as a delivery system for miRNA and siRNA in HCC in addition to the latest results achieved using this approach.

Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018292331240404070236
2024-05-02
2025-09-17
Loading full text...

Full text loading...

References

  1. BrayF. FerlayJ. SoerjomataramI. SiegelR.L. TorreL.A. JemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.201868639442410.3322/caac.2149230207593
    [Google Scholar]
  2. JemalA. BrayF. CenterM.M. FerlayJ. WardE. FormanD. Global cancer statistics.CA Cancer J. Clin.2011612699010.3322/caac.2010721296855
    [Google Scholar]
  3. HussainS.A. FerryD.R. El-GazzazG. MirzaD.F. JamesN.D. McMasterP. KerrD.J. Hepatocellular carcinoma.Ann. Oncol.200112216117210.1023/A:100837032482711300318
    [Google Scholar]
  4. ChenC.J. YuM.W. LiawY.F. Epidemiological characteristics and risk factors of hepatocellular carcinoma.J. Gastroenterol. Hepatol.1997129-10S294S30810.1111/j.1440‑1746.1997.tb00513.x9407350
    [Google Scholar]
  5. VillanuevaA. Hepatocellular Carcinoma.N. Engl. J. Med.2019380151450146210.1056/NEJMra171326330970190
    [Google Scholar]
  6. MarreroJ.A. KulikL.M. SirlinC.B. ZhuA.X. FinnR.S. AbecassisM.M. RobertsL.R. HeimbachJ.K. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the american association for the study of liver diseases.Hepatology201868272375010.1002/hep.2991329624699
    [Google Scholar]
  7. European Association For The Study Of The Liver European Organisation For Research And Treatment Of Cancer EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma.J. Hepatol.201256490894310.1016/j.jhep.2011.12.00122424438
    [Google Scholar]
  8. FornerA. ReigM. BruixJ. Hepatocellular carcinoma.Lancet2018391101271301131410.1016/S0140‑6736(18)30010‑229307467
    [Google Scholar]
  9. LlovetJ.M. RealM.I. MontañaX. PlanasR. CollS. AponteJ. AyusoC. SalaM. MuchartJ. SolàR. RodésJ. BruixJ. Barcelona Liver Cancer Group Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial.Lancet200235993191734173910.1016/S0140‑6736(02)08649‑X12049862
    [Google Scholar]
  10. LoC.M. NganH. TsoW.K. LiuC.L. LamC.M. PoonR.T.P. FanS.T. WongJ. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology20023551164117110.1053/jhep.2002.3315611981766
    [Google Scholar]
  11. LlovetJ. BruixJ. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival.Hepatology200337242944210.1053/jhep.2003.5004712540794
    [Google Scholar]
  12. LlovetJ.M. RicciS. MazzaferroV. HilgardP. GaneE. BlancJ.F. de OliveiraA.C. SantoroA. RaoulJ.L. FornerA. SchwartzM. PortaC. ZeuzemS. BolondiL. GretenT.F. GalleP.R. SeitzJ.F. BorbathI. HäussingerD. GiannarisT. ShanM. MoscoviciM. VoliotisD. BruixJ. SHARP Investigators Study Group Sorafenib in advanced hepatocellular carcinoma.N. Engl. J. Med.2008359437839010.1056/NEJMoa070885718650514
    [Google Scholar]
  13. ChengA.L. KangY.K. ChenZ. TsaoC.J. QinS. KimJ.S. LuoR. FengJ. YeS. YangT.S. XuJ. SunY. LiangH. LiuJ. WangJ. TakW.Y. PanH. BurockK. ZouJ. VoliotisD. GuanZ. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial.Lancet Oncol.2009101253410.1016/S1470‑2045(08)70285‑719095497
    [Google Scholar]
  14. KudoM. FinnR.S. QinS. HanK.H. IkedaK. PiscagliaF. BaronA. ParkJ.W. HanG. JassemJ. BlancJ.F. VogelA. KomovD. EvansT.R.J. LopezC. DutcusC. GuoM. SaitoK. KraljevicS. TamaiT. RenM. ChengA.L. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial.Lancet2018391101261163117310.1016/S0140‑6736(18)30207‑129433850
    [Google Scholar]
  15. BruixJ. QinS. MerleP. GranitoA. HuangY.H. BodokyG. PrachtM. YokosukaO. RosmorducO. BrederV. GerolamiR. MasiG. RossP.J. SongT. BronowickiJ.P. Ollivier-HourmandI. KudoM. ChengA.L. LlovetJ.M. FinnR.S. LeBerreM.A. BaumhauerA. MeinhardtG. HanG. RESORCE Investigators Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial.Lancet201738910064566610.1016/S0140‑6736(16)32453‑927932229
    [Google Scholar]
  16. YangC. ZhangH. ZhangL. ZhuA.X. BernardsR. QinW. WangC. Evolving therapeutic landscape of advanced hepatocellular carcinoma.Nat. Rev. Gastroenterol. Hepatol.202320420322210.1038/s41575‑022‑00704‑936369487
    [Google Scholar]
  17. WangC. PanC. YongH. WangF. BoT. ZhaoY. MaB. HeW. LiM. Emerging non-viral vectors for gene delivery.J. Nanobiotechnology202321127210.1186/s12951‑023‑02044‑537592351
    [Google Scholar]
  18. EgliM. ManoharanM. Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic Acids Res.20235162529257310.1093/nar/gkad06736881759
    [Google Scholar]
  19. LeeR.C. FeinbaumR.L. AmbrosV. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell199375584385410.1016/0092‑8674(93)90529‑Y8252621
    [Google Scholar]
  20. PaulP. ChakrabortyA. SarkarD. LangthasaM. RahmanM. BariM. SinghaR.K.S. MalakarA.K. ChakrabortyS. Interplay between miRNAs and human diseases.J. Cell. Physiol.201823332007201810.1002/jcp.2585428181241
    [Google Scholar]
  21. HaM. KimV.N. Regulation of microRNA biogenesis.Nat. Rev. Mol. Cell Biol.201415850952410.1038/nrm383825027649
    [Google Scholar]
  22. O’BrienJ. HayderH. ZayedY. PengC. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation.Front. Endocrinol.2018940210.3389/fendo.2018.0040230123182
    [Google Scholar]
  23. RoyB. GhoseS. BiswasS. Therapeutic strategies for miRNA delivery to reduce hepatocellular carcinoma.Semin. Cell Dev. Biol.202212413414410.1016/j.semcdb.2021.04.00633926792
    [Google Scholar]
  24. HuangS. HeX. The role of microRNAs in liver cancer progression.Br. J. Cancer2011104223524010.1038/sj.bjc.660601021102580
    [Google Scholar]
  25. XuX. TaoY. ShanL. ChenR. JiangH. QianZ. CaiF. MaL. YuY. The role of MicroRNAs in hepatocellular carcinoma.J. Cancer20189193557356910.7150/jca.2635030310513
    [Google Scholar]
  26. MorishitaA. OuraK. TadokoroT. FujitaK. TaniJ. MasakiT. MicroRNAs in the pathogenesis of hepatocellular carcinoma: A review.Cancers202113351410.3390/cancers1303051433572780
    [Google Scholar]
  27. KhareS. KhareT. RamanathanR. IbdahJ.A. Hepatocellular carcinoma: The role of MicroRNAs.Biomolecules202212564510.3390/biom1205064535625573
    [Google Scholar]
  28. WangJ. ChuY. XuM. ZhangX. ZhouY. XuM. miR-21 promotes cell migration and invasion of hepatocellular carcinoma by targeting KLF5.Oncol. Lett.20191722221222730675287
    [Google Scholar]
  29. ZhouY. RenH. DaiB. LiJ. ShangL. HuangJ. ShiX. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts.J. Exp. Clin. Cancer Res.201837132410.1186/s13046‑018‑0965‑230591064
    [Google Scholar]
  30. LiF. HuQ. PangZ. XuX. LncRNA MAGI2-AS3 upregulates cytokine signaling 1 by sponging miR-155 in non-small cell lung cancer.Cancer Biother. Radiopharm.2020351727610.1089/cbr.2019.289831910343
    [Google Scholar]
  31. LiN. CuiT. GuoW. WangD. MaoL. MiR-155-5p accelerates the metastasis of cervical cancer cell via targeting TP53INP1.OncoTargets Ther.2019123181319610.2147/OTT.S19309731118671
    [Google Scholar]
  32. LiuW.J. ZhaoY.P. ZhangT.P. ZhouL. CuiQ.C. ZhouW.X. YouL. ChenG. ShuH. MLH1 as a direct target of MiR-155 and a potential predictor of favorable prognosis in pancreatic cancer.J. Gastrointest. Surg.20131781399140510.1007/s11605‑013‑2230‑523715647
    [Google Scholar]
  33. ChenG. WangD. ZhaoX. CaoJ. ZhaoY. WangF. BaiJ. LuoD. LiL. miR-155-5p modulates malignant behaviors of hepatocellular carcinoma by directly targeting CTHRC1 and indirectly regulating GSK-3β-involved Wnt/β-catenin signaling.Cancer Cell Int.201717111810.1186/s12935‑017‑0469‑829234238
    [Google Scholar]
  34. CallegariE. ElaminB.K. GiannoneF. MilazzoM. AltavillaG. FornariF. GiacomelliL. D’AbundoL. FerracinM. BassiC. ZagattiB. CorràF. MiottoE. LupiniL. BolondiL. GramantieriL. CroceC.M. SabbioniS. NegriniM. Liver tumorigenicity promoted by microRNA-221 in a mouse transgenic model.Hepatology20125631025103310.1002/hep.2574722473819
    [Google Scholar]
  35. PineauP. VoliniaS. McJunkinK. MarchioA. BattistonC. TerrisB. MazzaferroV. LoweS.W. CroceC.M. DejeanA. miR-221 overexpression contributes to liver tumorigenesis.Proc. Natl. Acad. Sci. USA2010107126426910.1073/pnas.090790410720018759
    [Google Scholar]
  36. le SageC. NagelR. EganD.A. SchrierM. MesmanE. MangiolaA. AnileC. MairaG. MercatelliN. CiafrèS.A. FaraceM.G. AgamiR. Regulation of the p27Kip1 tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation.EMBO J.200726153699370810.1038/sj.emboj.760179017627278
    [Google Scholar]
  37. FornariF. GramantieriL. FerracinM. VeroneseA. SabbioniS. CalinG.A. GraziG.L. GiovanniniC. CroceC.M. BolondiL. NegriniM. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma.Oncogene200827435651566110.1038/onc.2008.17818521080
    [Google Scholar]
  38. YuanB. DongR. ShiD. ZhouY. ZhaoY. MiaoM. JiaoB. Down-regulation of miR-23b may contribute to activation of the TGF-β1/Smad3 signalling pathway during the termination stage of liver regeneration.FEBS Lett.2011585692793410.1016/j.febslet.2011.02.03121354414
    [Google Scholar]
  39. JiJ. ZhaoL. BudhuA. ForguesM. JiaH.L. QinL.X. YeQ.H. YuJ. ShiX. TangZ.Y. WangX.W. Let-7g targets collagen type I α2 and inhibits cell migration in hepatocellular carcinoma.J. Hepatol.201052569069710.1016/j.jhep.2009.12.02520338660
    [Google Scholar]
  40. MatsuuraK. De GiorgiV. SchechterlyC. WangR.Y. FarciP. TanakaY. AlterH.J. Circulating let-7 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C.Hepatology201664373274510.1002/hep.2866027227815
    [Google Scholar]
  41. DingJ. HuangS. WangY. TianQ. ZhaR. ShiH. WangQ. GeC. ChenT. ZhaoY. LiangL. LiJ. HeX. Genome-wide screening reveals that miR-195 targets the TNF-α/NF-κB pathway by down-regulating IκB kinase alpha and TAB3 in hepatocellular carcinoma.Hepatology201358265466610.1002/hep.2637823487264
    [Google Scholar]
  42. WangR. ZhaoN. LiS. FangJ.H. ChenM.X. YangJ. JiaW.H. YuanY. ZhuangS.M. MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42.Hepatology201358264265310.1002/hep.2637323468064
    [Google Scholar]
  43. ZhangM. WuJ. ZhangR. YangJ. ZhangQ. LiuB. miR-497 inhibits the carcinogenesis of hepatocellular carcinoma by targeting the Rictor/Akt signal pathway.Int. J. Clin. Exp. Pathol.20191261992200031934021
    [Google Scholar]
  44. XiongY. FangJ.H. YunJ.P. YangJ. ZhangY. JiaW.H. ZhuangS.M. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma.Hepatology201051383684520041405
    [Google Scholar]
  45. ChengD. DengJ. ZhangB. HeX. MengZ. LiG. YeH. ZhengS. WeiL. DengX. ChenR. ZhouJ. LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation.EBioMedicine20183615917010.1016/j.ebiom.2018.08.05530195653
    [Google Scholar]
  46. HsuS. WangB. KotaJ. YuJ. CostineanS. KutayH. YuL. BaiS. La PerleK. ChivukulaR.R. MaoH. WeiM. ClarkK.R. MendellJ.R. CaligiuriM.A. JacobS.T. MendellJ.T. GhoshalK. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver.J. Clin. Invest.201212282871288310.1172/JCI6353922820288
    [Google Scholar]
  47. Biselli-ChicoteP.M. OliveiraA.R.C.P. PavarinoE.C. Goloni-BertolloE.M. VEGF gene alternative splicing: Pro- and anti-angiogenic isoforms in cancer.J. Cancer Res. Clin. Oncol.2012138336337010.1007/s00432‑011‑1073‑222045472
    [Google Scholar]
  48. OliveiraA. Castanhole-NunesM. Biselli-ChicoteP. PavarinoÉ. SilvaR. SilvaR. Goloni-BertolloE.M. Differential expression of angiogenesis-related miRNAs and VEGFA in cirrhosis and hepatocellular carcinoma.Arch. Med. Sci.20201651150115710.5114/aoms.2020.9796732864004
    [Google Scholar]
  49. MeirsonT. Gil-HennH. SamsonA.O. Invasion and metastasis: the elusive hallmark of cancer.Oncogene20203992024202610.1038/s41388‑019‑1110‑131745295
    [Google Scholar]
  50. PanL. HuangS. HeR. RongM. DangY. ChenG. Decreased expression and clinical significance of miR-148a in hepatocellular carcinoma tissues.Eur. J. Med. Res.20141916810.1186/s40001‑014‑0068‑225444499
    [Google Scholar]
  51. FurutaM. KozakiK. TanakaS. AriiS. ImotoI. InazawaJ. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma.Carcinogenesis201031576677610.1093/carcin/bgp25019843643
    [Google Scholar]
  52. WangW. ZhaoL.J. TanY.X. RenH. QiZ.T. MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma.Carcinogenesis20123351113112010.1093/carcin/bgs11322362728
    [Google Scholar]
  53. CoulouarnC. FactorV.M. AndersenJ.B. DurkinM.E. ThorgeirssonS.S. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.Oncogene200928403526353610.1038/onc.2009.21119617899
    [Google Scholar]
  54. ZhangS. LiuQ. ZhangQ. LiuL. MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1.Oncol. Lett.20171445018502610.3892/ol.2017.674529085515
    [Google Scholar]
  55. HouX. YangL. JiangX. LiuZ. LiX. XieS. LiG. LiuJ. Role of microRNA-141-3p in the progression and metastasis of hepatocellular carcinoma cell.Int. J. Biol. Macromol.201912833133910.1016/j.ijbiomac.2019.01.14430695725
    [Google Scholar]
  56. NiJ.S. ZhengH. HuangZ.P. HongY.G. OuY.L. TaoY.P. WangM.C. WangZ.G. YangY. ZhouW.P. MicroRNA-197-3p acts as a prognostic marker and inhibits cell invasion in hepatocellular carcinoma.Oncol. Lett.20191722317232730675297
    [Google Scholar]
  57. ChangR.M. XiaoS. LeiX. YangH. FangF. YangL.Y. miRNA-487a promotes proliferation and metastasis in hepatocellular carcinoma.Clin. Cancer Res.201723102593260410.1158/1078‑0432.CCR‑16‑085127827315
    [Google Scholar]
  58. YauW.L. LamC.S.C. NgL. ChowA.K.M. ChanS.T.C. ChanJ.Y.K. WoJ.Y.H. NgK.T.P. ManK. PoonR.T.P. PangR.W.C. Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process.PLoS One201383e5788210.1371/journal.pone.005788223483935
    [Google Scholar]
  59. BaghbanR. RoshangarL. Jahanban-EsfahlanR. SeidiK. Ebrahimi-KalanA. JaymandM. KolahianS. JavaheriT. ZareP. Tumor microenvironment complexity and therapeutic implications at a glance.Cell Commun. Signal.20201815910.1186/s12964‑020‑0530‑432264958
    [Google Scholar]
  60. KondělkováK. VokurkováD. KrejsekJ. BorskáL. FialaZ. AndrýsC. Regulatory T cells (TREG) and their roles in immune system with respect to immunopathological disorders.Acta Med.2010532737710.14712/18059694.2016.6320672742
    [Google Scholar]
  61. YangP. LiQ.J. FengY. ZhangY. MarkowitzG.J. NingS. DengY. ZhaoJ. JiangS. YuanY. WangH.Y. ChengS.Q. XieD. WangX.F. TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.Cancer Cell201222329130310.1016/j.ccr.2012.07.02322975373
    [Google Scholar]
  62. LiA. ShuaiX. JiaZ. LiH. LiangX. SuD. GuoW. Ganoderma lucidum polysaccharide extract inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation and function by inducing microRNA-125b.J. Transl. Med.201513110010.1186/s12967‑015‑0465‑525889022
    [Google Scholar]
  63. FaruquFN XuL Al-JamalKT Preparation of exosomes for siRNA delivery to cancer cells.J. Vis. Exp.20185142
    [Google Scholar]
  64. ScaggianteB. DapasB. FarraR. GrassiM. PozzatoG. GiansanteC. GrassiG. GrassiG. Improving siRNA bio-distribution and minimizing side effects.Curr. Drug Metab.2011121112310.2174/13892001179452001721222588
    [Google Scholar]
  65. FarraR. GrassiM. GrassiG. DapasB. Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma.World J. Gastroenterol.201521308994900110.3748/wjg.v21.i30.899426290628
    [Google Scholar]
  66. FarraR. DapasB. PozzatoG. GiansanteC. HeidenreichO. UxaL. ZennaroC. GuarnieriG. GrassiG. Serum response factor depletion affects the proliferation of the hepatocellular carcinoma cells HepG2 and JHH6.Biochimie201092545546310.1016/j.biochi.2010.01.00720144681
    [Google Scholar]
  67. FarraR. DapasB. PozzatoG. ScaggianteB. AgostiniF. ZennaroC. GrassiM. RossoN. GiansanteC. FiottiN. GrassiG. Effects of E2F1–cyclin E1–E2 circuit down regulation in hepatocellular carcinoma cells.Dig. Liver Dis.201143121006101410.1016/j.dld.2011.07.00721831731
    [Google Scholar]
  68. HajiasgharzadehK. SomiM.H. ShanehbandiD. MokhtarzadehA. BaradaranB. Small interfering RNA–mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma.J. Cell. Physiol.201923443263327610.1002/jcp.2701530362510
    [Google Scholar]
  69. LiuH. ChenZ. JinW. BarveA. WanY.J.Y. ChengK. Silencing of α-complex protein-2 reverses alcohol- and cytokine-induced fibrogenesis in hepatic stellate cells.Liver Res.201711707910.1016/j.livres.2017.05.00328966795
    [Google Scholar]
  70. SongE. LeeS.K. WangJ. InceN. OuyangN. MinJ. ChenJ. ShankarP. LiebermanJ. RNA interference targeting Fas protects mice from fulminant hepatitis.Nat. Med.20039334735110.1038/nm82812579197
    [Google Scholar]
  71. HuangW. LiX. YiM. ZhuS. ChenW. Targeted delivery of si RNA against hepatitis B virus by pre S1 peptide molecular ligand.Hepatol. Res.201444889790610.1111/hepr.1218923799901
    [Google Scholar]
  72. MehdizadehA. SomiM.H. DarabiM. FarajniaS. AkbarzadehA. MontazersahebS. YousefiM. BonyadiM. Liposome-mediated RNA interference delivery against Erk1 and Erk2 does not equally promote chemosensitivity in human hepatocellular carcinoma cell line HepG2.Artif. Cells Nanomed. Biotechnol.20174581612161910.1080/21691401.2016.126911728058860
    [Google Scholar]
  73. ZhaoY. JianW. GaoW. ZhengY.X. WangY.K. ZhouZ.Q. ZhangH. WangC.J. RNAi silencing of c-Myc inhibits cell migration, invasion, and proliferation in HepG2 human hepatocellular carcinoma cell line: C-Myc silencing in hepatocellular carcinoma cell.Cancer Cell Int.20131312310.1186/1475‑2867‑13‑2323497309
    [Google Scholar]
  74. ChenJ. XiaH. ZhangX. KarthikS. PratapS.V. OoiL.L. HongW. HuiK.M. ECT2 regulates the Rho/ERK signalling axis to promote early recurrence in human hepatocellular carcinoma.J. Hepatol.20156261287129510.1016/j.jhep.2015.01.01425617497
    [Google Scholar]
  75. LeeY-H. JudgeA.D. SeoD. KitadeM. Gómez-QuirozL.E. IshikawaT. AndersenJ.B. KimB-K. MarquardtJ.U. RaggiC. AvitalI. ConnerE.A. MacLachlanI. FactorV.M. ThorgeirssonS.S. Molecular targeting of CSN5 in human hepatocellular carcinoma: A mechanism of therapeutic response.Oncogene201130404175418410.1038/onc.2011.12621499307
    [Google Scholar]
  76. YanX. ChuaM.S. HeJ. SoS.K. Small interfering RNA targeting CDC25B inhibits liver tumor growth in vitro and in vivo.Mol. Cancer2008711910.1186/1476‑4598‑7‑1918269767
    [Google Scholar]
  77. SassG. LeukelP. SchmitzV. RaskopfE. OckerM. NeureiterD. MeissnitzerM. TasikaE. TannapfelA. TiegsG. Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice.Int. J. Cancer200812361269127710.1002/ijc.2369518566988
    [Google Scholar]
  78. BogoradR.L. YinH. ZeigererA. NonakaH. RudaV.M. ZerialM. AndersonD.G. KotelianskyV. Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice.Nat. Commun.201451386910.1038/ncomms486924844798
    [Google Scholar]
  79. WangX. DingJ. FengY. WengL. ZhaoG. XiangJ. ZhangM. XingD. Targeting of growth factors in the treatment of hepatocellular carcinoma: The potentials of polysaccharides.Oncol. Lett.20171331509151710.3892/ol.2017.560228454283
    [Google Scholar]
  80. GaoJ. YuY. ZhangY. SongJ. ChenH. LiW. QianW. DengL. KouG. ChenJ. GuoY. EGFR-specific PEGylated immunoliposomes for active siRNA delivery in hepatocellular carcinoma.Biomaterials201233127028210.1016/j.biomaterials.2011.09.03521963149
    [Google Scholar]
  81. RaskopfE. VogtA. SauerbruchT. SchmitzV. siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo.J. Hepatol.200849697798410.1016/j.jhep.2008.07.02218845354
    [Google Scholar]
  82. XieB. XingR. ChenP. GouY. LiS. XiaoJ. DongJ. Down-regulation of c-Met expression inhibits human HCC cells growth and invasion by RNA interference.J. Surg. Res.2010162223123810.1016/j.jss.2009.04.03019765730
    [Google Scholar]
  83. KangD. HanZ. OhG.H. JooY. ChoiH.J. SongJ.J. Down-regulation of TGF-β expression sensitizes the resistance of hepatocellular carcinoma cells to sorafenib.Yonsei Med. J.201758589990910.3349/ymj.2017.58.5.89928792132
    [Google Scholar]
  84. ChenS. ZhengP. WangW. YiM. ChenP. CaiJ. LiJ. PengQ. BanY. ZhouY. ZengZ. LiX. XiongW. LiG. XiangB. Abberent expression of NOR1 protein in tumor associated macrophages contributes to the development of DEN-induced hepatocellular carcinoma.J. Cell. Physiol.201823365002501310.1002/jcp.2634929227538
    [Google Scholar]
  85. BerasainC. CastilloJ. PerugorriaM.J. LatasaM.U. PrietoJ. AvilaM.A. Inflammation and liver cancer: New molecular links.Ann. N. Y. Acad. Sci.20091155120622110.1111/j.1749‑6632.2009.03704.x19250206
    [Google Scholar]
  86. JingY. ShishkovA. PonnappaB.C. Inhibition of tumor necrosis factor alpha secretion in rat Kupffer cells by siRNA: In vivo efficacy of siRNA-liposomes.Biochim. Biophys. Acta, Gen. Subj.200817801344010.1016/j.bbagen.2007.09.01517964727
    [Google Scholar]
  87. HuangX. JianW. WuZ. ZhaoJ. WangH. LiW. XiaJ. Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation.Oncotarget20145145570558010.18632/oncotarget.214125015194
    [Google Scholar]
  88. ShiW. SuL. LiQ. SunL. LvJ. LiJ. ChengB. Suppression of toll-like receptor 2 expression inhibits the bioactivity of human hepatocellular carcinoma.Tumour Biol.201435109627963710.1007/s13277‑014‑2268‑324964964
    [Google Scholar]
  89. ShahnehF.Z. ValiyariS. AzadmehrA. HajiaghaeeR. YaripourS. BandehaghA. BaradaranB. Inhibition of growth and induction of apoptosis in fibrosarcoma cell lines by echinophora platyloba dc: In vitro analysis.Adv. Pharmacol. Sci.201320131710.1155/2013/51293123365566
    [Google Scholar]
  90. YuQ. LiuZ.Y. ChenQ. LinJ. Mcl-1 as a potential therapeutic target for human hepatocelluar carcinoma.J. Huazhong Univ. Sci. Technolog. Med. Sci.201636449450010.1007/s11596‑016‑1614‑727465322
    [Google Scholar]
  91. KuntzenC. SonucN. De ToniE.N. OpelzC. MuchaS.R. GerbesA.L. EichhorstS.T. Inhibition of c-Jun-N-terminal-kinase sensitizes tumor cells to CD95-induced apoptosis and induces G2/M cell cycle arrest.Cancer Res.200565156780678810.1158/0008‑5472.CAN‑04‑261816061660
    [Google Scholar]
  92. LuW.J. ChuaM.S. SoS.K. Suppressing N-Myc downstream regulated gene 1 reactivates senescence signaling and inhibits tumor growth in hepatocellular carcinoma.Carcinogenesis201435491592210.1093/carcin/bgt40124302615
    [Google Scholar]
  93. ZhangK. ChenJ. ChenD. HuangJ. FengB. HanS. ChenY. SongH. DeW. ZhuZ. WangR. ChenL. Aurora-A promotes chemoresistance in hepatocelluar carcinoma by targeting NF-kappaB/microRNA-21/PTEN signaling pathway.Oncotarget2014524129161293510.18632/oncotarget.268225428915
    [Google Scholar]
  94. MoralesA. ParísR. VillanuevaA. LlacunaL. García-RuizC. Fernández-ChecaJ.C. Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo.Oncogene200726690591610.1038/sj.onc.120983416862171
    [Google Scholar]
  95. KandaT. YokosukaO. ImazekiF. AraiM. SaishoH. Enhanced sensitivity of human hepatoma cells to 5-fluorouracil by small interfering RNA targeting Bcl-2.DNA Cell Biol.2005241280580910.1089/dna.2005.24.80516332177
    [Google Scholar]
  96. TakahashiY. NishikawaM. TakakuraY. Inhibition of tumor cell growth in the liver by RNA interference-mediated suppression of HIF-1α expression in tumor cells and hepatocytes.Gene Ther.200815857258210.1038/sj.gt.330310318273056
    [Google Scholar]
  97. LuX. QinW. LiJ. TanN. PanD. ZhangH. XieL. YaoG. ShuH. YaoM. WanD. GuJ. YangS. The growth and metastasis of human hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump.Cancer Res.200565156843684910.1158/0008‑5472.CAN‑04‑382216061667
    [Google Scholar]
  98. YuS.J. KangX.H. ZhangJ.N. WangH.M. XieT. WangW. WangS.J. Effects of small interfering RNA targeting heparanase-1 combined with heparin on invasiveness of mouse hepatocellular carcinoma cell lines.Chin. J. Cancer201029981682310.5732/cjc.009.1074620800024
    [Google Scholar]
  99. SalviA. AriciB. De PetroG. BarlatiS. Small interfering RNA urokinase silencing inhibits invasion and migration of human hepatocellular carcinoma cells.Mol. Cancer Ther.20043667167810.1158/1535‑7163.671.3.615210852
    [Google Scholar]
  100. LiC. WangJ. ZhangH. ZhuM. ChenF. HuY. LiuH. ZhuH. Interferon-stimulated Gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma.Oncotarget20145188429844110.18632/oncotarget.231625238261
    [Google Scholar]
  101. ShajariN. MansooriB. DavudianS. MohammadiA. BaradaranB. Overcoming the challenges of siRNA delivery: Nanoparticle strategies.Curr. Drug Deliv.2017141364610.2174/156720181366616081610540827538460
    [Google Scholar]
  102. AlshaerW. ZureigatH. Al KarakiA. Al-KadashA. GharaibehL. HatmalM.M. AljabaliA.A.A. AwidiA. siRNA: Mechanism of action, challenges, and therapeutic approaches.Eur. J. Pharmacol.202190517417810.1016/j.ejphar.2021.17417834044011
    [Google Scholar]
  103. HuangY. HongJ. ZhengS. DingY. GuoS. ZhangH. ZhangX. DuQ. LiangZ. Elimination pathways of systemically delivered siRNA.Mol. Ther.201119238138510.1038/mt.2010.26621119623
    [Google Scholar]
  104. JacksonA.L. LinsleyP.S. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application.Nat. Rev. Drug Discov.201091576710.1038/nrd301020043028
    [Google Scholar]
  105. BaloghJ. VictorD.III AshamE.H. BurroughsS.G. BoktourM. SahariaA. LiX. GhobrialM. MonsourH.Jr Hepatocellular carcinoma: A review.J. Hepatocell. Carcinoma20163415310.2147/JHC.S6114627785449
    [Google Scholar]
  106. ReischlD. ZimmerA. Drug delivery of siRNA therapeutics: Potentials and limits of nanosystems.Nanomedicine20095182010.1016/j.nano.2008.06.00118640078
    [Google Scholar]
  107. KanedaY. Gene therapy: A battle against biological barriers.Curr. Mol. Med.20011449349910.2174/156652401336351911899093
    [Google Scholar]
  108. BrownM.D. SchätzleinA.G. UchegbuI.F. Gene delivery with synthetic (non viral) carriers.Int. J. Pharm.20012291-212110.1016/S0378‑5173(01)00861‑411604253
    [Google Scholar]
  109. LundstromK. Viral vectors in gene therapy.Diseases2018624210.3390/diseases602004229883422
    [Google Scholar]
  110. LiX. LeY. ZhangZ. NianX. LiuB. YangX. Viral vector-based gene therapy.Int. J. Mol. Sci.2023249773610.3390/ijms2409773637175441
    [Google Scholar]
  111. ButtM. ZamanM. AhmadA. KhanR. MallhiT. HasanM. KhanY. HafeezS. MassoudE. RahmanM. CavaluS. Appraisal for the potential of viral and nonviral vectors in gene therapy: A review.Genes2022138137010.3390/genes1308137036011281
    [Google Scholar]
  112. AgencyE.M. Glybera.2017Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/glybera#:~:text=The%20marketing%20authorisation%20for%20Glybera,medicine%20on%208%20March%202004
  113. RamamoorthM. NarvekarA. Non viral vectors in gene therapy- An overview.J. Clin. Diagn. Res.201591GE01GE0610.7860/JCDR/2015/10443.539425738007
    [Google Scholar]
  114. XinY. HuangM. GuoW.W. HuangQ. ZhangL. JiangG. Nano-based delivery of RNAi in cancer therapy.Mol. Cancer201716113410.1186/s12943‑017‑0683‑y28754120
    [Google Scholar]
  115. RupaimooleR. SlackF.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases.Nat. Rev. Drug Discov.201716320322210.1038/nrd.2016.24628209991
    [Google Scholar]
  116. TakahashiR. Prieto-VilaM. KohamaI. OchiyaT. Development of mi RNA -based therapeutic approaches for cancer patients.Cancer Sci.201911041140114710.1111/cas.1396530729639
    [Google Scholar]
  117. ChenY. GaoD.Y. HuangL. In vivo delivery of miRNAs for cancer therapy: Challenges and strategies.Adv. Drug Deliv. Rev.20158112814110.1016/j.addr.2014.05.00924859533
    [Google Scholar]
  118. HosseinahliN. AghapourM. DuijfP.H.G. BaradaranB. Treating cancer with microRNA replacement therapy: A literature review.J. Cell. Physiol.201823385574558810.1002/jcp.2651429521426
    [Google Scholar]
  119. BocaS. GuleiD. ZimtaA.A. OnaciuA. MagdoL. TiguA.B. IonescuC. IrimieA. BuigaR. Berindan-NeagoeI. Nanoscale delivery systems for microRNAs in cancer therapy.Cell. Mol. Life Sci.20207761059108610.1007/s00018‑019‑03317‑931637450
    [Google Scholar]
  120. WilsonB. GeethaK.M. Lipid nanoparticles in the development of mRNA vaccines for COVID-19.J. Drug Deliv. Sci. Technol.20227410355310.1016/j.jddst.2022.10355335783677
    [Google Scholar]
  121. HaiderM. AbdinS.M. KamalL. OriveG. Nanostructured lipid carriers for delivery of chemotherapeutics: A review.Pharmaceutics202012328810.3390/pharmaceutics1203028832210127
    [Google Scholar]
  122. DhimanN. AwasthiR. SharmaB. KharkwalH. KulkarniG.T. Lipid nanoparticles as carriers for bioactive delivery.Front Chem.2021958011810.3389/fchem.2021.58011833981670
    [Google Scholar]
  123. JacobsF. WisseE. De GeestB. The role of liver sinusoidal cells in hepatocyte-directed gene transfer.Am. J. Pathol.20101761142110.2353/ajpath.2010.09013619948827
    [Google Scholar]
  124. MatsumuraY. MaedaH. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.Cancer Res.19864612 Pt 1638763922946403
    [Google Scholar]
  125. MaedaH. WuJ. SawaT. MatsumuraY. HoriK. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review.J. Control. Release2000651-227128410.1016/S0168‑3659(99)00248‑510699287
    [Google Scholar]
  126. IyerA.K. KhaledG. FangJ. MaedaH. Exploiting the enhanced permeability and retention effect for tumor targeting.Drug Discov. Today20061117-1881281810.1016/j.drudis.2006.07.00516935749
    [Google Scholar]
  127. YuanF. DellianM. FukumuraD. LeunigM. BerkD.A. TorchilinV.P. JainR.K. Vascular permeability in a human tumor xenograft: Molecular size dependence and cutoff size.Cancer Res.19955517375237567641188
    [Google Scholar]
  128. BöttgerR. PauliG. ChaoP.H. AL FayezN. HohenwarterL. LiS.D. Lipid-based nanoparticle technologies for liver targeting.Adv. Drug Deliv. Rev.2020154-1557910110.1016/j.addr.2020.06.01732574575
    [Google Scholar]
  129. LlovetJ.M. BruixJ. Molecular targeted therapies in hepatocellular carcinoma.Hepatology20084841312132710.1002/hep.2250618821591
    [Google Scholar]
  130. MishraN. YadavN.P. RaiV.K. SinhaP. YadavK.S. JainS. AroraS. Efficient hepatic delivery of drugs: Novel strategies and their significance.BioMed Res. Int.2013201312010.1155/2013/38218424286077
    [Google Scholar]
  131. LiM. ZhangW. WangB. GaoY. SongZ. ZhengQ.C. Ligand-based targeted therapy: A novel strategy for hepatocellular carcinoma.Int. J. Nanomedicine2016115645566910.2147/IJN.S11572727920520
    [Google Scholar]
  132. XueH. GuoP. WenW.C. WongH. Lipid-based nanocarriers for RNA delivery.Curr. Pharm. Des.201521223140314710.2174/138161282166615053116454026027572
    [Google Scholar]
  133. NóbregaC. MendonçaL. MatosC.A. Barriers to gene delivery.A Handbook of Gene and Cell Therapy. NóbregaC. MendonçaL. MatosC.A. ChamSpringer International Publishing20209110110.1007/978‑3‑030‑41333‑0_4
    [Google Scholar]
  134. GavrilovK. SaltzmanW.M. Therapeutic siRNA: Principles, challenges, and strategies.Yale J. Biol. Med.201285218720022737048
    [Google Scholar]
  135. PathakK. KeshriL. ShahM. Lipid nanocarriers: Influence of lipids on product development and pharmacokinetics.Crit. Rev. Ther. Drug Carrier Syst.201128435739310.1615/CritRevTherDrugCarrierSyst.v28.i4.2021967401
    [Google Scholar]
  136. XueH.Y. LiuS. WongH.L. Nanotoxicity: A key obstacle to clinical translation of siRNA-based nanomedicine.Nanomedicine20149229531210.2217/nnm.13.20424552562
    [Google Scholar]
  137. LappalainenK. JääskeläinenI. SyrjänenK. UrttiA. SyrjänenS. Comparison of cell proliferation and toxicity assays using two cationic liposomes.Pharm. Res.19941181127113110.1023/A:10189327147457971713
    [Google Scholar]
  138. WuJ. LizarzaburuM.E. KurthM.J. LiuL. WegeH. ZernM.A. NantzM.H. Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents.Bioconjug. Chem.200112225125710.1021/bc000097e11312686
    [Google Scholar]
  139. AberleA.M. TablinF. ZhuJ. WalkerN.J. GruenertD.C. NantzM.H. A novel tetraester construct that reduces cationic lipid-associated cytotoxicity. Implications for the onset of cytotoxicity.Biochemistry199837186533654010.1021/bi98011549572871
    [Google Scholar]
  140. ZhangJ. LiuF. HuangL. Implications of pharmacokinetic behavior of lipoplex for its inflammatory toxicity.Adv. Drug Deliv. Rev.200557568969810.1016/j.addr.2004.12.00415757755
    [Google Scholar]
  141. TousignantJ.D. GatesA.L. IngramL.A. JohnsonC.L. NietupskiJ.B. ChengS.H. EastmanS.J. ScheuleR.K. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid: Plasmid DNA complexes in mice.Hum. Gene Ther.200011182493251310.1089/1043034005020798411119421
    [Google Scholar]
  142. TanY. HuangL. Overcoming the inflammatory toxicity of cationic gene vectors.J. Drug Target.200210215316010.1080/1061186029001675712074542
    [Google Scholar]
  143. MishraS. WebsterP. DavisM.E. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles.Eur. J. Cell Biol.20048339711110.1078/0171‑9335‑0036315202568
    [Google Scholar]
  144. DamsE.T. LavermanP. OyenW.J. StormG. ScherphofG.L. van Der MeerJ.W. CorstensF.H. BoermanO.C. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes.J. Pharmacol. Exp. Ther.200029231071107910688625
    [Google Scholar]
  145. BombelliC. GiansantiL. LucianiP. ManciniG. Gemini surfactant based carriers in gene and drug delivery.Curr. Med. Chem.200916217118310.2174/09298670978700280819149569
    [Google Scholar]
  146. FangY. XueJ. GaoS. LuA. YangD. JiangH. HeY. ShiK. Cleavable PEGylation: A strategy for overcoming the “PEG dilemma” in efficient drug delivery.Drug Deliv.2017242223210.1080/10717544.2017.138845129069920
    [Google Scholar]
  147. LvD. LiY. ZhangW. AlvarezA.A. SongL. TangJ. GaoW.Q. HuB. ChengS.Y. FengH. TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma.Nat. Commun.201781145410.1038/s41467‑017‑01731‑w29129908
    [Google Scholar]
  148. ZhiD. ZhangS. WangB. ZhaoY. YangB. YuS. Transfection efficiency of cationic lipids with different hydrophobic domains in gene delivery.Bioconjug. Chem.201021456357710.1021/bc900393r20121120
    [Google Scholar]
  149. SimbergD. WeismanS. TalmonY. BarenholzY. DOTAP (and other cationic lipids): Chemistry, biophysics, and transfection.Crit. Rev. Ther. Drug Carrier Syst.200421425731710.1615/CritRevTherDrugCarrierSyst.v21.i4.1015638468
    [Google Scholar]
  150. PontiF. CampolungoM. MelchioriC. BonoN. CandianiG. Cationic lipids for gene delivery: Many players, one goal.Chem. Phys. Lipids202123510503210.1016/j.chemphyslip.2020.10503233359210
    [Google Scholar]
  151. HaqueM.E. McIntoshT.J. LentzB.R. Influence of lipid composition on physical properties and peg-mediated fusion of curved and uncurved model membrane vesicles: “Nature’s own” fusogenic lipid bilayer.Biochemistry200140144340434810.1021/bi002030k11284690
    [Google Scholar]
  152. AkincA. GoldbergM. QinJ. DorkinJ.R. Gamba-VitaloC. MaierM. JayaprakashK.N. JayaramanM. RajeevK.G. ManoharanM. KotelianskyV. RöhlI. LeshchinerE.S. LangerR. AndersonD.G. Development of lipidoid-siRNA formulations for systemic delivery to the liver.Mol. Ther.200917587287910.1038/mt.2009.3619259063
    [Google Scholar]
  153. LoveK.T. MahonK.P. LevinsC.G. WhiteheadK.A. QuerbesW. DorkinJ.R. QinJ. CantleyW. QinL.L. RacieT. Frank-KamenetskyM. YipK.N. AlvarezR. SahD.W.Y. de FougerollesA. FitzgeraldK. KotelianskyV. AkincA. LangerR. AndersonD.G. Lipid-like materials for low-dose, in vivo gene silencing.Proc. Natl. Acad. Sci. USA201010751864186910.1073/pnas.091060310620080679
    [Google Scholar]
  154. JayaramanM. AnsellS.M. MuiB.L. TamY.K. ChenJ. DuX. ButlerD. EltepuL. MatsudaS. NarayanannairJ.K. RajeevK.G. HafezI.M. AkincA. MaierM.A. TracyM.A. CullisP.R. MaddenT.D. ManoharanM. HopeM.J. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.Angew. Chem. Int. Ed.201251348529853310.1002/anie.20120326322782619
    [Google Scholar]
  155. RossiJ.J. RNAi therapeutics: SNALPing siRNAs in vivo.Gene Ther.200613758358410.1038/sj.gt.330266117526070
    [Google Scholar]
  156. GreishK. Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting.Methods Mol. Biol.2010624253710.1007/978‑1‑60761‑609‑2_320217587
    [Google Scholar]
  157. XueH.Y. WongH.L. Solid lipid-PEI hybrid nanocarrier: An integrated approach to provide extended, targeted, and safer siRNA therapy of prostate cancer in an all-in-one manner.ACS Nano2011597034704710.1021/nn201659z21838301
    [Google Scholar]
  158. MokhtariehA.A. CheongS. KimS. ChungB.H. LeeM.K. Asymmetric liposome particles with highly efficient encapsulation of siRNA and without nonspecific cell penetration suitable for target-specific delivery.Biochim. Biophys. Acta Biomembr.2012181871633164110.1016/j.bbamem.2012.03.01622465072
    [Google Scholar]
  159. TyagiN. AroraS. DeshmukhS.K. SinghS. MarimuthuS. SinghA.P. Exploiting nanotechnology for the development of microrna-based cancer therapeutics.J. Biomed. Nanotechnol.2016121284210.1166/jbn.2016.217227301170
    [Google Scholar]
  160. DhanasekaranR. Gabay-RyanM. BaylotV. LaiI. MosleyA. HuangX. ZabludoffS. LiJ. KaimalV. KarmaliP. FelsherD.W. Anti-miR-17 therapy delays tumorigenesis in MYC-driven hepatocellular carcinoma (HCC).Oncotarget2018955517552810.18632/oncotarget.2234229464015
    [Google Scholar]
  161. HuangX. MagnusJ. KaimalV. KarmaliP. LiJ. WallsM. PrudenteR. SungE. SorourianM. LeeR. DavisS. YangX. EstrellaH. LeeE.C. ChauB.N. PavlicekA. ZabludoffS. Lipid nanoparticle–mediated delivery of anti-miR-17 family oligonucleotide suppresses hepatocellular carcinoma growth.Mol. Cancer Ther.201716590591310.1158/1535‑7163.MCT‑16‑061328167506
    [Google Scholar]
  162. ZhangM. ZhouX. WangB. YungB.C. LeeL.J. GhoshalK. LeeR.J. Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.J. Control. Release2013168325126110.1016/j.jconrel.2013.03.02023567045
    [Google Scholar]
  163. TsaiW.C. HsuS.D. HsuC.S. LaiT.C. ChenS.J. ShenR. HuangY. ChenH.C. LeeC.H. TsaiT.F. HsuM.T. WuJ.C. HuangH.D. ShiaoM.S. HsiaoM. TsouA.P. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis.J. Clin. Invest.201212282884289710.1172/JCI6345522820290
    [Google Scholar]
  164. WangX. YuB. RenW. MoX. ZhouC. HeH. JiaH. WangL. JacobS.T. LeeR.J. GhoshalK. LeeL.J. Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid nanoparticle formulations.J. Control. Release2013172369069810.1016/j.jconrel.2013.09.02724121065
    [Google Scholar]
  165. FanY.P. LiaoJ.Z. LuY.Q. TianD.A. YeF. ZhaoP.X. XiangG.Y. TangW.X. HeX.X. MiR-375 and doxorubicin co-delivered by liposomes for combination therapy of hepatocellular carcinoma.Mol. Ther. Nucleic Acids2017718118910.1016/j.omtn.2017.03.01028624193
    [Google Scholar]
  166. XuF. LiaoJ.Z. XiangG.Y. ZhaoP.X. YeF. ZhaoQ. HeX.X. MiR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma.Cancer Med.20176365166110.1002/cam4.101628135055
    [Google Scholar]
  167. YangT. ZhaoP. RongZ. LiB. XueH. YouJ. HeC. LiW. HeX. LeeR.J. MaX. XiangG. Anti-tumor efficiency of lipid-coated cisplatin nanoparticles co-loaded with MicroRNA-375.Theranostics20166114215410.7150/thno.1313026722380
    [Google Scholar]
  168. DaigeC PriddyL WigginsJ Nelligan-DavisT EnzlerD VadnagaraK MRX34, a liposomal miR-34 mimic and potential first-in-class microRNA therapeutic: Activity in animal models of liver cancer.Clin. Oncol.20163415_supple1407610.1200/JCO.2016.34.15_suppl.e14076
    [Google Scholar]
  169. AndreakosE. RauchhausU. StavropoulosA. EndertG. WendischV. BenahmedA.S. GiaglisS. KarrasJ. LeeS. GausH. BennettC.F. WilliamsR.O. SiderasP. PanznerS. Amphoteric liposomes enable systemic antigen-presenting cell–directed delivery of CD40 antisense and are therapeutically effective in experimental arthritis.Arthritis Rheum.2009604994100510.1002/art.2443419333921
    [Google Scholar]
  170. BegM.S. BrennerA.J. SachdevJ. BoradM. KangY.K. StoudemireJ. SmithS. BaderA.G. KimS. HongD.S. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors.Invest. New Drugs201735218018810.1007/s10637‑016‑0407‑y27917453
    [Google Scholar]
  171. HongD.S. KangY.K. BoradM. SachdevJ. EjadiS. LimH.Y. BrennerA.J. ParkK. LeeJ.L. KimT.Y. ShinS. BecerraC.R. FalchookG. StoudemireJ. MartinD. KelnarK. PeltierH. BonatoV. BaderA.G. SmithS. KimS. O’NeillV. BegM.S. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours.Br. J. Cancer2020122111630163710.1038/s41416‑020‑0802‑132238921
    [Google Scholar]
  172. LinX. LiL. WangR. WilcoxD. ZhaoX. SongJ. HuangX. HansenT.M. DandeP. WadaC. HubbardR.D. KohlbrennerW.M. FesikS.W. ShenY. A robust in vivo positive-readout system for monitoring siRNA delivery to xenograft tumors.RNA201117460361210.1261/rna.254601121321186
    [Google Scholar]
  173. YounisM.A. KhalilI.A. Abd ElwakilM.M. HarashimaH. A multifunctional lipid-based nanodevice for the highly specific codelivery of sorafenib and midkine siRNA to hepatic cancer cells.Mol. Pharm.20191694031404410.1021/acs.molpharmaceut.9b0073831403802
    [Google Scholar]
  174. YounisM.A. KhalilI.A. ElewaY.H.A. KonY. HarashimaH. Ultra-small lipid nanoparticles encapsulating sorafenib and midkine-siRNA selectively-eradicate sorafenib-resistant hepatocellular carcinoma in vivo.J. Control. Release202133133534910.1016/j.jconrel.2021.01.02133484779
    [Google Scholar]
  175. LiL. WangR. WilcoxD. SarthyA. LinX. HuangX. TianL. DandeP. HubbardR.D. HansenT.M. WadaC. ZhaoX. KohlbrennerW.M. FesikS.W. ShenY. Developing lipid nanoparticle-based siRNA therapeutics for hepatocellular carcinoma using an integrated approach.Mol. Cancer Ther.201312112308231810.1158/1535‑7163.MCT‑12‑0983‑T23943805
    [Google Scholar]
  176. LeboeufD. AbakumovaT. PrikazchikovaT. RhymL. AndersonD.G. ZatsepinT.S. PiatkovK.I. Downregulation of the Arg/N-degron pathway sensitizes cancer cells to chemotherapy in vivo.Mol. Ther.20202841092110410.1016/j.ymthe.2020.01.02132087767
    [Google Scholar]
  177. LeeY.H. SeoD. ChoiK.J. AndersenJ.B. WonM.A. KitadeM. Gómez-QuirozL.E. JudgeA.D. MarquardtJ.U. RaggiC. ConnerE.A. MacLachlanI. FactorV.M. ThorgeirssonS.S. Antitumor effects in hepatocarcinoma of isoform-selective inhibition of HDAC2.Cancer Res.201474174752476110.1158/0008‑5472.CAN‑13‑353124958469
    [Google Scholar]
  178. GaneshS. KoserM.L. CyrW.A. ChopdaG.R. TaoJ. ShuiX. YingB. ChenD. PandyaP. ChipumuroE. SiddiqueeZ. CraigK. LaiC. DudekH. MongaS.P. WangW. BrownB.D. AbramsM.T. Direct pharmacological inhibition of β-catenin by RNA interference in tumors of diverse origin.Mol. Cancer Ther.20161592143215410.1158/1535‑7163.MCT‑16‑030927390343
    [Google Scholar]
  179. FitamantJ. KottakisF. BenhamoucheS. TianH.S. ChuvinN. ParachoniakC.A. NagleJ.M. PereraR.M. LapougeM. DeshpandeV. ZhuA.X. LaiA. MinB. HoshidaY. AvruchJ. SiaD. CampreciósG. McClatcheyA.I. LlovetJ.M. MorrisseyD. RajL. BardeesyN. YAP inhibition restores hepatocyte differentiation in advanced HCC, leading to tumor regression.Cell Rep.201510101692170710.1016/j.celrep.2015.02.02725772357
    [Google Scholar]
  180. ZhangS. NguyenL.H. ZhouK. TuH.C. SehgalA. NassourI. LiL. GopalP. GoodmanJ. SingalA.G. YoppA. ZhangY. SiegwartD.J. ZhuH. Knockdown of anillin actin binding protein blocks cytokinesis in hepatocytes and reduces liver tumor development in mice without affecting regeneration.Gastroenterology201815451421143410.1053/j.gastro.2017.12.01329274368
    [Google Scholar]
  181. ZhaoY. HuangL. Lipid nanoparticles for gene delivery.Adv. Genet.201488133610.1016/B978‑0‑12‑800148‑6.00002‑X25409602
    [Google Scholar]
  182. MashimaR. TakadaS. Lipid nanoparticles: A novel gene delivery technique for clinical application.Curr. Issues Mol. Biol.202244105013502710.3390/cimb4410034136286056
    [Google Scholar]
/content/journals/cdd/10.2174/0115672018292331240404070236
Loading
/content/journals/cdd/10.2174/0115672018292331240404070236
Loading

Data & Media loading...

Supplements

Supplementary material isavailable on the publisher’s web site along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test