Skip to content
2000
Volume 25, Issue 7
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Gene silencing through RNA interference (RNAi) technology has provided forceful therapeutic modalities to specific knockdown of the genes' expression related to diseases. Small interfering RNAs (siRNAs) can start a process that specifically degrades and silences the expression of cognate mRNAs. These RNA interference processes could effectively adjust many biological processes, including immune responses. Dendritic cells (DCs) are specialist antigen-presenting cells with potent functions in regulating innate and adaptive immunity. SiRNAs performed vital roles in coordinating immune processes mediated by DCs. This review describes the findings that shed light on the significance of siRNAs in DC immune regulation and highlight their potential applications for improving DC-based immunotherapies.

Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240303370240530120450
2024-06-07
2025-10-24
Loading full text...

Full text loading...

References

  1. TucciF. GalimbertiS. NaldiniL. ValsecchiM.G. AiutiA. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.Nat. Commun.2022131131510.1038/s41467‑022‑28762‑2 35288539
    [Google Scholar]
  2. LocatelliF. ThompsonA.A. KwiatkowskiJ.L. Betibeglogene autotemcel gene therapy for non–β0/β0 genotype β-thalassemia.N. Engl. J. Med.2022386541542710.1056/NEJMoa2113206 34891223
    [Google Scholar]
  3. MoudryP. ChromaK. BursacS. VolarevicS. BartekJ. RNA-interference screen for p53 regulators unveils a role of WDR75 in ribosome biogenesis.Cell Death Differ.202229368769610.1038/s41418‑021‑00882‑0 34611297
    [Google Scholar]
  4. SwerdlowD.I. RiderD.A. YavariA. Wikström LindholmM. CampionG.V. NissenS.E. Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: The emerging potential of RNA interference therapeutics.Cardiovasc. Res.202211851218123110.1093/cvr/cvab100 33769464
    [Google Scholar]
  5. de Paula BrandãoP.R. Titze-de-AlmeidaS.S. Titze-de-AlmeidaR. Leading RNA interference therapeutics part 2: Silencing delta-aminolevulinic acid synthase 1, with a focus on givosiran.Mol. Diagn. Ther.2020241616810.1007/s40291‑019‑00438‑6 31792921
    [Google Scholar]
  6. ChenX. MangalaL.S. Rodriguez-AguayoC. KongX. Lopez-BeresteinG. SoodA.K. RNA interference-based therapy and its delivery systems.Cancer Metastasis Rev.201837110712410.1007/s10555‑017‑9717‑6 29243000
    [Google Scholar]
  7. GutbrodM.J. MartienssenR.A. Conserved chromosomal functions of RNA interference.Nat. Rev. Genet.202021531133110.1038/s41576‑019‑0203‑6 32051563
    [Google Scholar]
  8. El-AwadyA.R. ElashiryM. MorandiniA.C. MeghilM.M. CutlerC.W. Dendritic cells a critical link to alveolar bone loss and systemic disease risk in periodontitis: Immunotherapeutic implications.Periodontol2022891415010.1111/prd.12428 35244951
    [Google Scholar]
  9. ShahverdiM. MasoumiJ. GhorbaninezhadF. The modulatory role of dendritic cell-T cell cross-talk in breast cancer: Challenges and prospects.Adv. Med. Sci.202267235336310.1016/j.advms.2022.09.001 36116207
    [Google Scholar]
  10. HuJ.L. OmofoyeO.A. RudnickJ.D. A phase I study of autologous dendritic cell vaccine pulsed with allogeneic stem-like cell line lysate in patients with newly diagnosed or recurrent glioblastoma.Clin. Cancer Res.202228468969610.1158/1078‑0432.CCR‑21‑2867 34862245
    [Google Scholar]
  11. KochE.A.T. SchaftN. KummerM. A one-armed phase I dose escalation trial design: Personalized vaccination with IKKβ-matured, RNA-loaded dendritic cells for metastatic uveal melanoma.Front. Immunol.20221378523110.3389/fimmu.2022.785231
    [Google Scholar]
  12. SuzukiM. ZhengX. ZhangX. A novel allergen-specific therapy for allergy using CD40-silenced dendritic cells.J. Allergy Clin. Immunol.2010125373774310.1016/j.jaci.2009.11.042
    [Google Scholar]
  13. SubramanyaS. ArmantM. SalkowitzJ.R. Enhanced induction of HIV-specific cytotoxic T lymphocytes by dendritic cell-targeted delivery of SOCS-1 siRNA.Mol. Ther.201018112028203710.1038/mt.2010.148 20648001
    [Google Scholar]
  14. MasjediA. AhmadiA. GhaniS. Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy.Nanomedicine20202910224010.1016/j.nano.2020.102240 32553948
    [Google Scholar]
  15. JiangM. ÖsterlundP. WesteniusV. Efficient inhibition of avian and seasonal influenza A viruses by a virus-specific Dicer-substrate small interfering RNA swarm in human monocyte-derived macrophages and dendritic cells.J. Virol.2019934e019161810.1128/JVI.01916‑18 30463970
    [Google Scholar]
  16. Sæbøe-LarssenS. SioudM. Improving Dendritic Cell Cancer Vaccine Potency Using RNA Interference.In: RNA Interference and CRISPR Technologies Methods in Molecular Biology.Springer202024925810.1007/978‑1‑0716‑0290‑4_14
    [Google Scholar]
  17. HassanniaH. Ghasemi ChaleshtariM. AtyabiF. Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine.Immunology20201591758710.1111/imm.13126 31587253
    [Google Scholar]
  18. YuZ. WuM. HuangY. Single-component lipid nanoparticles for engineering SOCS1 gene-silenced dendritic cells to boost tumor immunotherapy.Biomater. Sci.202211126327710.1039/D2BM01549H 36440740
    [Google Scholar]
  19. AhmedM.S. ByeonS.E. JeongY. Dab2, a negative regulator of DC immunogenicity, is an attractive molecular target for DC-based immunotherapy.OncoImmunology201541e98455010.4161/2162402X.2014.984550 25949867
    [Google Scholar]
  20. ZhengX. KoropatnickJ. ChenD. Silencing IDO in dendritic cells: A novel approach to enhance cancer immunotherapy in a murine breast cancer model.Int. J. Cancer2013132496797710.1002/ijc.27710 22870862
    [Google Scholar]
  21. ConroyH. GalvinK.C. HigginsS.C. MillsK.H.G. Gene silencing of TGF-β1 enhances antitumor immunity induced with a dendritic cell vaccine by reducing tumor-associated regulatory T cells.Cancer Immunol. Immunother.201261342543110.1007/s00262‑011‑1188‑y 22193988
    [Google Scholar]
  22. HuizingaT. Treatment of autoimmune arthritis using RNA interference-modulated dendritic cells.Int J Adv Rheumatol201083116117[Commentary]
    [Google Scholar]
  23. ZhangM.M. BahalR. RasmussenT.P. ManautouJ.E. ZhongX. The growth of siRNA-based therapeutics: Updated clinical studies.Biochem. Pharmacol.202118911443210.1016/j.bcp.2021.114432 33513339
    [Google Scholar]
  24. HattabD. GazzaliA.M. BakhtiarA. Clinical advances of siRNA-based nanotherapeutics for cancer treatment.Pharmaceutics2021137100910.3390/pharmaceutics13071009 34371702
    [Google Scholar]
  25. HuB. ZhongL. WengY. Therapeutic siRNA: State of the art.Signal Transduct. Target. Ther.20205110110.1038/s41392‑020‑0207‑x 32561705
    [Google Scholar]
  26. DuaK. WadhwaR. SinghviG. The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress.Drug Dev. Res.201980671473010.1002/ddr.21571 31691339
    [Google Scholar]
  27. ChenW. FengP. LiuK. WuM. LinH. Computational identification of small interfering RNA targets in SARS-CoV-2.Virol. Sin.202035335936110.1007/s12250‑020‑00221‑6 32297156
    [Google Scholar]
  28. CharbeN.B. AmnerkarN.D. RameshB. Small interfering RNA for cancer treatment: Overcoming hurdles in delivery.Acta Pharm. Sin. B202010112075210910.1016/j.apsb.2020.10.005 33304780
    [Google Scholar]
  29. ZhangX. ZhangM. ZhouM. Tetrahedral-framework nucleic acids carry small interfering RNA to downregulate toll-like receptor 2 gene expression for the treatment of sepsis.ACS Appl. Mater. Interfaces20221456442645210.1021/acsami.1c23708 35080860
    [Google Scholar]
  30. MendonçaM.C.P. KontA. AburtoM.R. CryanJ.F. O’DriscollC.M. Advances in the design of (nano) formulations for delivery of antisense oligonucleotides and small interfering RNA: Focus on the central nervous system.Mol. Pharm.20211841491150610.1021/acs.molpharmaceut.0c01238 33734715
    [Google Scholar]
  31. BanerjeeY. Pantea StoianA. CiceroA.F.G. Inclisiran: A small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia.Expert Opin. Drug Saf.202221192010.1080/14740338.2022.1988568 34596005
    [Google Scholar]
  32. FriedrichM. PfeiferG. BinderS. Selection and validation of siRNAs preventing uptake and replication of SARS-CoV-2.Front. Bioeng. Biotechnol.20221080187010.3389/fbioe.2022.801870 35309990
    [Google Scholar]
  33. de JongA. DirvenR.J. BoenderJ. Ex vivo improvement of a von Willebrand disease type 2A phenotype using an allele-specific small-interfering RNA.Thromb. Haemost.2020120111569157910.1055/s‑0040‑1715442 32803740
    [Google Scholar]
  34. ShinJ.W. ShinA. ParkS.S. LeeJ.M. Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington’s disease.Mol. Ther. Methods Clin. Dev.202225849510.1016/j.omtm.2022.03.001 35356757
    [Google Scholar]
  35. MiglioreL. GalvagniF. PierantozziE. SorrentinoV. RossiD. Allele-specific silencing by RNAi of R92Q and R173W mutations in cardiac troponin T.Exp. Biol. Med. (Maywood)20222471080581410.1177/15353702211072453 35067102
    [Google Scholar]
  36. MurrayJ.K. Identification and optimization of a minor allele-specific siRNA to prevent PNPLA3 I148M-driven nonalcoholic fatty liver disease.Nucleic Acid Ther.2021315324340
    [Google Scholar]
  37. KorenM.J. MoriartyP.M. BaumS.J. Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a).Nat. Med.20222819610310.1038/s41591‑021‑01634‑w 35027752
    [Google Scholar]
  38. SuranaR. Phase I study of mesenchymal stem cell (MSC)-derived exosomes with KRASG12D siRNA in patients with metastatic pancreatic cancer harboring a KRASG12D mutation.J. Clin. Oncol.202240410.1200/JCO.2022.40.4_suppl.TPS633
    [Google Scholar]
  39. ZhaoQ. FengH. YangZ. The central role of a two‐way positive feedback pathway in molecular targeted therapies‐mediated pyroptosis in anaplastic thyroid cancer.Clin. Transl. Med.2022122e72710.1002/ctm2.727 35184413
    [Google Scholar]
  40. ZhanQ. YiK. CuiX. Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy.Neuro-oncol.202224111871188310.1093/neuonc/noac071 35312010
    [Google Scholar]
  41. PasiK.J. LissitchkovT. MamonovV. Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran—Results of the phase 1 inhibitor cohort.J. Thromb. Haemost.20211961436144610.1111/jth.15270 33587824
    [Google Scholar]
  42. RangwalaH.S. FatimaH. RiazF. RangwalaB.S. Comment on “Inclisiran siRNA technology in the management of dyslipidemia: A narrative review of clinical trials”.Curr. Probl. Cardiol.202449610251610.1016/j.cpcardiol.2024.102516 38492614
    [Google Scholar]
  43. OzcanG. OzpolatB. ColemanR.L. SoodA.K. Lopez-BeresteinG. Preclinical and clinical development of siRNA-based therapeutics.Adv. Drug Deliv. Rev.20158710811910.1016/j.addr.2015.01.007 25666164
    [Google Scholar]
  44. MansooriB. MohammadiA. Shir JangS. BaradaranB. Mechanisms of immune system activation in mammalians by small interfering RNA (siRNA).Artif. Cells Nanomed. Biotechnol.20164471589159610.3109/21691401.2015.1102738 26497011
    [Google Scholar]
  45. MengZ. LuM. RNA interference-induced innate immunity, off-target effect, or immune adjuvant?Front. Immunol.2017833110.3389/fimmu.2017.00331 28386261
    [Google Scholar]
  46. SchaeferA.K. Pathogen-and microbial-associated molecular patterns (PAMPs/MAMPs) and the innate immune response in Crohn’s disease.In: Immunity and Inflammation in Health and Disease.Elsevier201817518710.1016/B978‑0‑12‑805417‑8.00014‑7
    [Google Scholar]
  47. XiaoY. DriedonksT. WitwerK.W. WangQ. YinH. How does an RNA selfie work? EV‐associated RNA in innate immunity as self or danger.J. Extracell. Vesicles202091179351510.1080/20013078.2020.1793515 32944182
    [Google Scholar]
  48. GiuriniE.F. MadonnaM.B. ZlozaA. GuptaK.H. Microbial-derived toll-like receptor agonism in cancer treatment and progression.Cancers20221412292310.3390/cancers14122923 35740589
    [Google Scholar]
  49. HuT. Improving siRNA specificity with Guanosine Nucleobase Modifications: TLR8 Response and miRNA-like Off-Target Effect.DavisUniversity of California2019
    [Google Scholar]
  50. SioudM. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization.J. Mol. Biol.200534851079109010.1016/j.jmb.2005.03.013 15854645
    [Google Scholar]
  51. HornungV. Guenthner-BillerM. BourquinC. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7.Nat. Med.200511326327010.1038/nm1191 15723075
    [Google Scholar]
  52. JudgeA.D. SoodV. ShawJ.R. FangD. McClintockK. MacLachlanI. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA.Nat. Biotechnol.200523445746210.1038/nbt1081 15778705
    [Google Scholar]
  53. TakahashiT. NakanoY. OnomotoK. YoneyamaM. Ui-TeiK. Virus sensor RIG-I represses RNA interference by interacting with TRBP through LGP2 in mammalian cells.Genes201891051110.3390/genes9100511 30347765
    [Google Scholar]
  54. RackleyL. RNA fibers as optimized nanoscaffolds for siRNA coordination and reduced immunological recognition.In: Therapeutic RNA Nanotechnology.Jenny Stanford Publishing2021943969
    [Google Scholar]
  55. SabadoR.L. BalanS. BhardwajN. Dendritic cell-based immunotherapy.Cell Res.2017271749510.1038/cr.2016.157 28025976
    [Google Scholar]
  56. WorbsT. HammerschmidtS.I. FörsterR. Dendritic cell migration in health and disease.Nat. Rev. Immunol.2017171304810.1038/nri.2016.116 27890914
    [Google Scholar]
  57. JengL.B. LiaoL.Y. ShihF.Y. TengC.F. Dendritic-cell-vaccine-based immunotherapy for hepatocellular carcinoma: Clinical trials and recent preclinical studies.Cancers20221418438010.3390/cancers14184380 36139542
    [Google Scholar]
  58. JonnyJ. PutrantoT.A. SitepuE.C. Dendritic cell vaccine as a potential strategy to end the COVID-19 pandemic. Why should it be Ex Vivo?Expert Rev. Vaccines202221811111120
    [Google Scholar]
  59. AoZ. WangL. AziziH. OlukitibiT.A. KobingerG. YaoX. Development and evaluation of an ebola virus glycoprotein mucin-like domain replacement system as a new dendritic cell-targeting vaccine approach against HIV-1.J. Virol.20219515e02368e2010.1128/JVI.02368‑20 34011553
    [Google Scholar]
  60. ShimizuJ. SudaT. YoshiokaT. KosugiA. FujiwaraH. HamaokaT. Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.J. Immunol.198914231053105910.4049/jimmunol.142.3.1053 2464022
    [Google Scholar]
  61. ZouJ. ShimizuJ. IkegameK. TakiuchiH. FujiwaraH. HamaokaT. Tumor-immunotherapy with the use of tumor-antigen-pulsed antigen-presenting cells.Cancer Immunol. Immunother.19923511610.1007/BF01741047 1611618
    [Google Scholar]
  62. GuoZ. Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer.NPJ Precis. Oncol.2022613410.1038/s41698‑022‑00279‑3
    [Google Scholar]
  63. WangQ.T. NieY. SunS.N. Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients.Cancer Immunol. Immunother.20206971375138710.1007/s00262‑020‑02496‑w 32078016
    [Google Scholar]
  64. NortonT. Lentiviral vector-based dendritic cell vaccine suppresses hiv replication in humanized mice.Mol. Ther.201927596097310.1016/j.ymthe.2019.03.008
    [Google Scholar]
  65. FlatekvalGF SioudM Modulation of dendritic cell maturation and function with mono‐ and bifunctional small interfering RNAs targeting indoleamine 2,3‐dioxygenase. Immunology20091281pt2)(Suppl.e8374810.1111/j.1365‑2567.2009.03093.x19740345
    [Google Scholar]
  66. LiuY. XuP. LiuH. Silencing IDO2 in dendritic cells: A novel strategy to strengthen cancer immunotherapy in a murine lung cancer model.Int. J. Oncol.202057258759710.3892/ijo.2020.5073 32468023
    [Google Scholar]
  67. SmithN. VidalainP.O. NisoleS. HerbeuvalJ.P. An efficient method for gene silencing in human primary plasmacytoid dendritic cells: Silencing of the TLR7/IRF-7 pathway as a proof of concept.Sci. Rep.2016612989110.1038/srep29891 27412723
    [Google Scholar]
  68. PrechtelA.T. TurzaN.M. TheodoridisA.A. SteinkassererA. CD83 knockdown in monocyte-derived dendritic cells by small interfering RNA leads to a diminished T cell stimulation.J. Immunol.200717895454546410.4049/jimmunol.178.9.5454 17442926
    [Google Scholar]
  69. TatipartiK. SauS. KashawS. IyerA. siRNA delivery strategies: A comprehensive review of recent developments.Nanomaterials2017747710.3390/nano7040077 28379201
    [Google Scholar]
  70. KimH.J. KimA. MiyataK. KataokaK. Recent progress in development of siRNA delivery vehicles for cancer therapy.Adv. Drug Deliv. Rev.2016104617710.1016/j.addr.2016.06.011 27352638
    [Google Scholar]
  71. WangJ. LuZ. WientjesM.G. AuJ.L.S. Delivery of siRNA therapeutics: Barriers and carriers.AAPS J.201012449250310.1208/s12248‑010‑9210‑4 20544328
    [Google Scholar]
  72. HausseckerD. Current issues of RNAi therapeutics delivery and development.J. Control. Release2014195495410.1016/j.jconrel.2014.07.056 25111131
    [Google Scholar]
  73. KobayashiH. WatanabeR. ChoykeP.L. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target?Theranostics201441818910.7150/thno.7193 24396516
    [Google Scholar]
  74. MindellJ.A. Lysosomal acidification mechanisms.Annu. Rev. Physiol.2012741698610.1146/annurev‑physiol‑012110‑142317 22335796
    [Google Scholar]
  75. QiuS. AdemaC.M. LaneT. A computational study of off-target effects of RNA interference.Nucleic Acids Res.20053361834184710.1093/nar/gki324 15800213
    [Google Scholar]
  76. GaoH. ChengR. SantosH.A. Nanoparticle‐mediated siRNA delivery systems for cancer therapy.View2021232020011110.1002/VIW.20200111
    [Google Scholar]
  77. KulkarniJ.A. WitzigmannD. ChenS. CullisP.R. van der MeelR. Lipid nanoparticle technology for clinical translation of siRNA therapeutics.Acc. Chem. Res.20195292435244410.1021/acs.accounts.9b00368 31397996
    [Google Scholar]
  78. WittrupA. LiebermanJ. Knocking down disease: A progress report on siRNA therapeutics.Nat. Rev. Genet.201516954355210.1038/nrg3978 26281785
    [Google Scholar]
  79. WhiteheadK.A. LangerR. AndersonD.G. Knocking down barriers: Advances in siRNA delivery.Nat. Rev. Drug Discov.20098212913810.1038/nrd2742 19180106
    [Google Scholar]
  80. SettenR.L. RossiJ.J. HanS. The current state and future directions of RNAi-based therapeutics.Nat. Rev. Drug Discov.201918642144610.1038/s41573‑019‑0017‑4 30846871
    [Google Scholar]
  81. ShenL. Evel-KablerK. StrubeR. ChenS.Y. Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity.Nat. Biotechnol.200422121546155310.1038/nbt1035 15558048
    [Google Scholar]
  82. KatakowskiJ.A. MukherjeeG. WilnerS.E. Delivery of siRNAs to dendritic cells using DEC205-targeted lipid nanoparticles to inhibit immune responses.Mol. Ther.201624114615510.1038/mt.2015.175 26412590
    [Google Scholar]
  83. HeoM.B. ChoM.Y. LimY.T. Polymer nanoparticles for enhanced immune response: Combined delivery of tumor antigen and small interference RNA for immunosuppressive gene to dendritic cells.Acta Biomater.20141052169217610.1016/j.actbio.2013.12.050 24394635
    [Google Scholar]
  84. ZhengX. VladauC. ZhangX. A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation.Blood2009113122646265410.1182/blood‑2008‑04‑151191 19164600
    [Google Scholar]
  85. RosaliaR.A. CruzL.J. van DuikerenS. CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses.Biomaterials201540889710.1016/j.biomaterials.2014.10.053 25465442
    [Google Scholar]
  86. YooY.J. LeeC.H. ParkS.H. LimY.T. Nanoparticle-based delivery strategies of multifaceted immunomodulatory RNA for cancer immunotherapy.J. Control. Release202234356458310.1016/j.jconrel.2022.01.047 35124126
    [Google Scholar]
  87. MaininiF. EcclesM.R. Lipid and polymer-based nanoparticle siRNA delivery systems for cancer therapy.Molecules20202511269210.3390/molecules25112692 32532030
    [Google Scholar]
  88. HariS.K. GaubaA. ShrivastavaN. TripathiR.M. JainS.K. PandeyA.K. Polymeric micelles and cancer therapy: An ingenious multimodal tumor-targeted drug delivery system.Drug Deliv. Transl. Res.202313113516310.1007/s13346‑022‑01197‑4 35727533
    [Google Scholar]
  89. JonesM.C. LerouxJ.C. Polymeric micelles – a new generation of colloidal drug carriers.Eur. J. Pharm. Biopharm.199948210111110.1016/S0939‑6411(99)00039‑9 10469928
    [Google Scholar]
  90. TorchilinV. Multifunctional nanocarriers.Adv. Drug Deliv. Rev.200658141532155510.1016/j.addr.2006.09.009 17092599
    [Google Scholar]
  91. SuttonD. NasongklaN. BlancoE. GaoJ. Functionalized micellar systems for cancer targeted drug delivery.Pharm. Res.20072461029104610.1007/s11095‑006‑9223‑y 17385025
    [Google Scholar]
  92. BaillyN. ThomasM. KlumpermanB. Poly(N-vinylpyrrolidone)-block-poly(vinyl acetate) as a drug delivery vehicle for hydrophobic drugs.Biomacromolecules201213124109411710.1021/bm301410d 23116120
    [Google Scholar]
  93. KimD.H. VitolE.A. LiuJ. Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles.Langmuir201329247425743210.1021/la3044158 23351096
    [Google Scholar]
  94. WilliamsH.D. TrevaskisN.L. CharmanS.A. Strategies to address low drug solubility in discovery and development.Pharmacol. Rev.201365131549910.1124/pr.112.005660 23383426
    [Google Scholar]
  95. TorchilinV.P. Targeted polymeric micelles for delivery of poorly soluble drugs.Cell. Mol. Life Sci.20046119-202549255910.1007/s00018‑004‑4153‑5 15526161
    [Google Scholar]
  96. TorchilinV.P. Micellar nanocarriers: Pharmaceutical perspectives.Pharm. Res.200624111610.1007/s11095‑006‑9132‑0 17109211
    [Google Scholar]
  97. JhaveriA.M. TorchilinV.P. Multifunctional polymeric micelles for delivery of drugs and siRNA.Front. Pharmacol.201457710.3389/fphar.2014.00077 24795633
    [Google Scholar]
  98. LuJ. Advanced strategies to evade the mononuclear phagocyte system clearance of nanomaterials.In: Exploration.Wiley Online Library2023
    [Google Scholar]
  99. TorchilinV. Tumor delivery of macromolecular drugs based on the EPR effect.Adv. Drug Deliv. Rev.201163313113510.1016/j.addr.2010.03.011 20304019
    [Google Scholar]
  100. MebarekN. VicenteR. Aubert-PouësselA. Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells.Eur. J. Pharm. Biopharm.20159221622710.1016/j.ejpb.2015.03.013 25796349
    [Google Scholar]
  101. MarquezA.R. MaduC.O. LuY. An overview of various carriers for siRNA delivery.Oncomedicine20183485810.7150/oncm.25785
    [Google Scholar]
  102. Bin UmairM. AkusaF.N. KashifH. Seerat-E-Fatima, Butt F. Viruses as tools in gene therapy, vaccine development, and cancer treatment.Arch. Virol.2022167613871404
    [Google Scholar]
  103. ButtM. ZamanM. AhmadA. Appraisal for the potential of viral and nonviral vectors in gene therapy: A review.Genes2022138137010.3390/genes13081370 36011281
    [Google Scholar]
  104. StewartS.A. DykxhoornD.M. PalliserD. Lentivirus-delivered stable gene silencing by RNAi in primary cells.RNA20039449350110.1261/rna.2192803 12649500
    [Google Scholar]
  105. LundstromK. Viral vectors applied for RNAi-based antiviral therapy.Viruses202012992410.3390/v12090924 32842491
    [Google Scholar]
  106. MiloneM.C. O’DohertyU. Clinical use of lentiviral vectors.Leukemia20183271529154110.1038/s41375‑018‑0106‑0 29654266
    [Google Scholar]
  107. EwerK. SebastianS. SpencerA.J. GilbertS. HillA.V.S. LambeT. Chimpanzee adenoviral vectors as vaccines for outbreak pathogens.Hum. Vaccin. Immunother.201713123020303210.1080/21645515.2017.1383575 29083948
    [Google Scholar]
  108. SnyderR.O. Adeno‐associated virus‐mediated gene delivery.J. Gene Med.19991316617510.1002/(SICI)1521‑2254(199905/06)1:3<166:AID‑JGM34>3.0.CO;2‑Z
    [Google Scholar]
  109. GaoG. VandenbergheL. WilsonJ. New recombinant serotypes of AAV vectors.Curr. Gene Ther.20055328529710.2174/1566523054065057 15975006
    [Google Scholar]
  110. ShegokarR. Al ShaalL. MishraP.R. SiRNA delivery: Challenges and role of carrier systems.Pharmazie2011665313318 21699063
    [Google Scholar]
  111. FollenziA. SantambrogioL. AnnoniA. Immune responses to lentiviral vectors.Curr. Gene Ther.20077530631510.2174/156652307782151515 17979677
    [Google Scholar]
  112. ShahryariA. BurtscherI. NazariZ. LickertH. Engineering gene therapy: Advances and barriers.Adv. Ther. (Weinh.)202149210004010.1002/adtp.202100040
    [Google Scholar]
  113. WangD. TaiP.W.L. GaoG. Adeno-associated virus vector as a platform for gene therapy delivery.Nat. Rev. Drug Discov.201918535837810.1038/s41573‑019‑0012‑9 30710128
    [Google Scholar]
  114. RanjitS. KissoonN. Dengue hemorrhagic fever and shock syndromes.Pediatr. Crit. Care Med.20111219010010.1097/PCC.0b013e3181e911a7 20639791
    [Google Scholar]
  115. ZhangW. SingamR. HellermannG. Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery.Genet. Vaccines Ther.200421810.1186/1479‑0556‑2‑8 15301687
    [Google Scholar]
  116. VisserJ. van Boxel-DezaireA. MethorstD. BruntT. de KloetE.R. NagelkerkenL. Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro.Blood199891114255426410.1182/blood.V91.11.4255 9596674
    [Google Scholar]
  117. de SmedtT. van MechelenM. De BeckerG. UrbainJ. LeoO. MoserM. Effect of interleukin‐10 on dendritic cell maturation and function.Eur. J. Immunol.19972751229123510.1002/eji.1830270526 9174615
    [Google Scholar]
  118. YangA.S. LattimeE.C. Tumor-induced interleukin 10 suppresses the ability of splenic dendritic cells to stimulate CD4 and CD8 T-cell responses.Cancer Res.200363921502157 12727833
    [Google Scholar]
  119. MittalS.K. ChoK.J. IshidoS. RocheP.A. Interleukin 10 (IL-10)-mediated Immunosuppression.J. Biol. Chem.201529045271582716710.1074/jbc.M115.682708 26408197
    [Google Scholar]
  120. ChhabraA. ChakrabortyN.G. MukherjiB. Silencing of endogenous IL-10 in human dendritic cells leads to the generation of an improved CTL response against human melanoma associated antigenic epitope, MART-1 27-35.Clin. Immunol.2008126325125910.1016/j.clim.2007.11.011 18249038
    [Google Scholar]
  121. BolhassaniA. KhavariA. OrafaZ. Electroporation-advantages and drawbacks for delivery of drug, gene and vaccine.In: Application of nanotechnology in drug delivery.20143699710.5772/58376
    [Google Scholar]
  122. MellottA.J. ForrestM.L. DetamoreM.S. Physical non-viral gene delivery methods for tissue engineering.Ann. Biomed. Eng.201341344646810.1007/s10439‑012‑0678‑1 23099792
    [Google Scholar]
  123. PrechtelA.T. TurzaN.M. TheodoridisA.A. KummerM. SteinkassererA. Small interfering RNA (siRNA) delivery into monocyte-derived dendritic cells by electroporation.J. Immunol. Methods20063111-213915210.1016/j.jim.2006.01.021 16556448
    [Google Scholar]
  124. SioudM. Optimized siRNA delivery into primary immune cells using electroporation.Methods Mol. Biol.2020211511913110.1007/978‑1‑0716‑0290‑4_7
    [Google Scholar]
  125. WangH. MooneyD.J. Biomaterial-assisted targeted modulation of immune cells in cancer treatment.Nat. Mater.201817976177210.1038/s41563‑018‑0147‑9 30104668
    [Google Scholar]
  126. SatoT. KatagiriK. KubotaY. OgawaT. In vitro sperm production from mouse spermatogonial stem cell lines using an organ culture method.Nat. Protoc.20138112098210410.1038/nprot.2013.138 24091557
    [Google Scholar]
  127. JantschJ. TurzaN. VolkeM. Small interfering RNA (siRNA) delivery into murine bone marrow-derived dendritic cells by electroporation.J. Immunol. Methods20083371717710.1016/j.jim.2008.04.004 18514219
    [Google Scholar]
  128. ShahabipourF. BanachM. SahebkarA. Exosomes as nanocarriers for siRNA delivery: Paradigms and challenges.Arch. Med. Sci.2016661324132610.5114/aoms.2016.62911 27904525
    [Google Scholar]
  129. ShamshiripourP. RahnamaM. NikoobakhtM. RadV.F. MoradiA.R. AhmadvandD. Extracellular vesicles derived from dendritic cells loaded with VEGF-A siRNA and doxorubicin reduce glioma angiogenesis in vitro.J. Control. Release202436912814510.1016/j.jconrel.2024.03.042 38522817
    [Google Scholar]
  130. AmiriA. BagherifarR. Ansari DezfouliE. KiaieS.H. JafariR. RamezaniR. Exosomes as bio-inspired nanocarriers for RNA delivery: Preparation and applications.J. Transl. Med.202220112510.1186/s12967‑022‑03325‑7 35287692
    [Google Scholar]
  131. UeharaK. HarumotoT. MakinoA. Targeted delivery to macrophages and dendritic cells by chemically modified mannose ligand-conjugated siRNA.Nucleic Acids Res.20225094840485910.1093/nar/gkac308 35524566
    [Google Scholar]
  132. Mastelic-GavilletB. BalintK. BoudousquieC. GannonP.O. KandalaftL.E. Personalized dendritic cell vaccines—recent breakthroughs and encouraging clinical results.Front. Immunol.20191076610.3389/fimmu.2019.00766 31031762
    [Google Scholar]
  133. BelderbosR.A. AertsJ.G.J.V. VromanH. Enhancing dendritic cell therapy in solid tumors with immunomodulating conventional treatment.Mol. Ther. Oncolytics201913678110.1016/j.omto.2019.03.007 31020037
    [Google Scholar]
  134. KheshtiA.M.S. HajizadehF. BarshidiA. RETRACTED ARTICLE: Combination cancer immunotherapy with dendritic cell vaccine and nanoparticles loaded with interleukin-15 and anti-beta-catenin siRNA significantly inhibits cancer growth and induces anti-tumor immune response.Pharm. Res.202239235336710.1007/s11095‑022‑03169‑2 35166995
    [Google Scholar]
  135. BarshidiA. KarpishehV. NoukabadiF.K. Dual blockade of PD-1 and LAG3 immune checkpoints increases dendritic cell vaccine mediated T cell responses in breast cancer model.Pharm. Res.20223981851186610.1007/s11095‑022‑03297‑9 35715669
    [Google Scholar]
  136. GhorbaninezhadF. AsadzadehZ. MasoumiJ. Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: From bench to bedside.Life Sci.202229712046610.1016/j.lfs.2022.120466 35271882
    [Google Scholar]
  137. HwangW. JungK. JeonY. YunS. KimT.W. ChoiI. Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors.Vaccine2010291344410.1016/j.vaccine.2010.10.027 20974308
    [Google Scholar]
  138. KurtulusS. Checkpoint blockade immunotherapy induces dynamic changes in PD-1− CD8+ tumor-infiltrating T cells.Immunity2019501181194
    [Google Scholar]
  139. SerratìS. GuidaM. Di FonteR. Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma.Mol. Cancer20222112010.1186/s12943‑021‑01490‑9 35042524
    [Google Scholar]
  140. HuiE. CheungJ. ZhuJ. T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition.Science201735563321428143310.1126/science.aaf1292 28280247
    [Google Scholar]
  141. KamphorstA.O. WielandA. NastiT. Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent.Science201735563321423142710.1126/science.aaf0683 28280249
    [Google Scholar]
  142. OhS.A. WuD.C. CheungJ. PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer.Nat. Can.20201768169110.1038/s43018‑020‑0075‑x 35122038
    [Google Scholar]
  143. MayouxM. RollerA. PulkoV. Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy.Sci. Transl. Med.202012534eaav743110.1126/scitranslmed.aav7431 32161104
    [Google Scholar]
  144. RotteA. Combination of CTLA-4 and PD-1 blockers for treatment of cancer.J. Exp. Clin. Cancer Res.201938125510.1186/s13046‑019‑1259‑z 31196207
    [Google Scholar]
  145. ZhangH. DaiZ. WuW. Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.J. Exp. Clin. Cancer Res.202140118410.1186/s13046‑021‑01987‑7 34088360
    [Google Scholar]
  146. EsmailyM. MasjediA. HallajS. Blockade of CTLA-4 increases anti-tumor response inducing potential of dendritic cell vaccine.J. Control. Release2020326637410.1016/j.jconrel.2020.06.017 32580042
    [Google Scholar]
  147. YangJ.C. HughesM. KammulaU. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis.J. Immunother.200730882583010.1097/CJI.0b013e318156e47e 18049334
    [Google Scholar]
  148. YangR. ElsaadiS. MisundK. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade.J. Immunother. Cancer202081e00061010.1136/jitc‑2020‑000610 32409420
    [Google Scholar]
  149. PerrotI. Blocking antibodies targeting the CD39/CD73 immunosuppressive pathway unleash immune responses in combination cancer therapies.Cell reports201927824112425
    [Google Scholar]
  150. AlzamelyK.O. HajizadehF. HeydariM. Combined inhibition of CD73 and ZEB1 by Arg-Gly-Asp (RGD)-targeted nanoparticles inhibits tumor growth.Colloids Surf. B Biointerfaces202119711142110.1016/j.colsurfb.2020.111421 33130525
    [Google Scholar]
  151. KingR.J. ShuklaS.K. HeC. CD73 induces GM-CSF/MDSC-mediated suppression of T cells to accelerate pancreatic cancer pathogenesis.Oncogene202241797198210.1038/s41388‑021‑02132‑6 35001076
    [Google Scholar]
  152. PiovesanD. TanJ.B.L. BeckerA. Targeting CD73 with AB680 (Quemliclustat), a novel and potent small molecule CD73 inhibitor, restores immune functionality and facilitates anti-tumor immunity.Mol. Cancer Ther.202221694895910.1158/1535‑7163.MCT‑21‑0802 35405741
    [Google Scholar]
  153. Jadidi-NiaraghF. AtyabiF. RastegariA. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice.J. Control. Release2017246465910.1016/j.jconrel.2016.12.012 27993599
    [Google Scholar]
  154. KamaiT. KijimaT. TsuzukiT. Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival.Cancer Immunol. Immunother.20217072009202110.1007/s00262‑020‑02843‑x 33416945
    [Google Scholar]
  155. SugiuraD. MaruhashiT. OkazakiI. Restriction of PD-1 function by cis -PD-L1/CD80 interactions is required for optimal T cell responses.Science2019364644055856610.1126/science.aav7062 31000591
    [Google Scholar]
  156. Karoon KianiF. IzadiS. Ansari DezfouliE. Simultaneous silencing of the A2aR and PD-1 immune checkpoints by siRNA-loaded nanoparticles enhances the immunotherapeutic potential of dendritic cell vaccine in tumor experimental models.Life Sci.202228812016610.1016/j.lfs.2021.120166 34813798
    [Google Scholar]
  157. NordeW.J. MaasF. HoboW. PD-1/PD-L1 interactions contribute to functional T-cell impairment in patients who relapse with cancer after allogeneic stem cell transplantation.Cancer Res.201171155111512210.1158/0008‑5472.CAN‑11‑0108 21659460
    [Google Scholar]
  158. van der WaartA.B. FredrixH. van der VoortR. SchaapN. HoboW. DolstraH. siRNA silencing of PD-1 ligands on dendritic cell vaccines boosts the expansion of minor histocompatibility antigen-specific CD8+ T cells in NOD/SCID/IL2Rg(null) mice.Cancer Immunol. Immunother.201564564565410.1007/s00262‑015‑1668‑6 25724840
    [Google Scholar]
  159. HoboW. NovobrantsevaT.I. FredrixH. Improving dendritic cell vaccine immunogenicity by silencing PD-1 ligands using siRNA-lipid nanoparticles combined with antigen mRNA electroporation.Cancer Immunol. Immunother.201362228529710.1007/s00262‑012‑1334‑1 22903385
    [Google Scholar]
  160. PengS. KimT.W. LeeJ.H. Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances antigen-specific immune responses by prolonging dendritic cell life.Hum. Gene Ther.200516558459310.1089/hum.2005.16.584 15916483
    [Google Scholar]
  161. MedemaJ.P. SchuurhuisD.H. ReaD. Expression of the serpin serine protease inhibitor 6 protects dendritic cells from cytotoxic T lymphocyte-induced apoptosis: Differential modulation by T helper type 1 and type 2 cells.J. Exp. Med.2001194565766810.1084/jem.194.5.657 11535633
    [Google Scholar]
  162. XuH.Y. LiN. YaoN. CD8+ Tcells stimulated by exosomes derived from RenCa cells mediate specific immune responses through the FasL/Fas signaling pathway and, combined with GM CSF and IL 12, enhance the anti-renal cortical adenocarcinoma effect.Oncol. Rep.201942286687910.3892/or.2019.7208 31233203
    [Google Scholar]
  163. SelenkoN. MajdicO. DraxlerS. CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells.Leukemia200115101619162610.1038/sj.leu.2402226 11587221
    [Google Scholar]
  164. KimJ.H. KangT.H. NohK.H. Enhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8+ T cell-mediated cell death.Immunol. Lett.20091221586710.1016/j.imlet.2008.12.006 19135479
    [Google Scholar]
  165. ShehzadiS. JavedM. UllahA. Bilal WaqarA. Iftikhar ShahF. UllahS. In-vitro augmentation of mesenchymal stem cells by using adult bovine serum.Curr. Stem Cell Res. Ther.20231910.2174/011574888X260118230927050143 37861050
    [Google Scholar]
  166. KangT.H. LeeJ.H. NohK.H. Enhancing dendritic cell vaccine potency by combining a BAK/BAX siRNA‐mediated antiapoptotic strategy to prolong dendritic cell life with an intracellular strategy to target antigen to lysosomal compartments.Int. J. Cancer200712081696170310.1002/ijc.22377 17230516
    [Google Scholar]
  167. WangT. JiangQ. ChanC. Inhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR.Blood2009113132906291310.1182/blood‑2008‑08‑176354 19164597
    [Google Scholar]
  168. LebsonL. WangT. JiangQ. WhartenbyK.A. Induction of the glucocorticoid-induced leucine zipper gene limits the efficacy of dendritic cell vaccines.Cancer Gene Ther.201118856357010.1038/cgt.2011.23 21546924
    [Google Scholar]
  169. Rodríguez-GonzálezJ. Wilkins-RodríguezA.A. Gutiérrez-KobehL. Involvement of Akt and the antiapoptotic protein Bcl‐xL in the inhibition of apoptosis of dendritic cells by Leishmania mexicana.Parasite Immunol.2022447e1291710.1111/pim.12917 35340042
    [Google Scholar]
  170. XieJ. QianJ. YangJ. WangS. FreemanM.E.III YiQ. Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells.Exp. Hematol.200533556457210.1016/j.exphem.2005.03.001 15850834
    [Google Scholar]
  171. KimJ.H. KangT.H. NohK.H. Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN.Immunol. Lett.20101341475410.1016/j.imlet.2010.08.008 20727912
    [Google Scholar]
  172. KimJ.H. KangT.H. NohK.H. Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency.Clin. Exp. Immunol.2011165218018910.1111/j.1365‑2249.2011.04410.x 21592111
    [Google Scholar]
  173. AhnY-H. HongS-O. KimJ.H. The siRNA cocktail targeting interleukin 10 receptor and transforming growth factor-β receptor on dendritic cells potentiates tumour antigen-specific CD8+ T cell immunity.Clin. Exp. Immunol.2015181116417810.1111/cei.12620 25753156
    [Google Scholar]
  174. CorintiS. AlbanesiC. la SalaA. PastoreS. GirolomoniG. Regulatory activity of autocrine IL-10 on dendritic cell functions.J. Immunol.200116674312431810.4049/jimmunol.166.7.4312 11254683
    [Google Scholar]
  175. ThepmaleeC. PanyaA. JunkingM. ChieochansinT. YenchitsomanusP. Inhibition of IL-10 and TGF-β receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells.Hum. Vaccin. Immunother.20181461423143110.1080/21645515.2018.1431598 29420117
    [Google Scholar]
  176. EndoR. NakamuraT. KawakamiK. SatoY. HarashimaH. The silencing of indoleamine 2,3-dioxygenase 1 (IDO1) in dendritic cells by siRNA-loaded lipid nanoparticles enhances cell-based cancer immunotherapy.Sci. Rep.2019911133510.1038/s41598‑019‑47799‑w 31383907
    [Google Scholar]
  177. LiS.S. YangM. ChenY.P. Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure.Mol. Immunol.2018101101810.1016/j.molimm.2018.05.016 29852455
    [Google Scholar]
  178. HeM. ChenX. LuoM. Suppressor of cytokine signaling 1 inhibits the maturation of dendritic cells involving the nuclear factor kappa B signaling pathway in the glioma microenvironment.Clin. Exp. Immunol.20202021475910.1111/cei.13476 32516488
    [Google Scholar]
  179. LiaoS. ChenJ. ZhangL.Y. ZhangJ. SunP.P. Ou-YangY. Effects of SOCS1-overexpressing dendritic cells on Th17- and Treg-related cytokines in COPD mice.BMC Pulm. Med.202222114510.1186/s12890‑022‑01931‑1 35428280
    [Google Scholar]
  180. SubramanyaS. KimS.S. AbrahamS. Targeted delivery of small interfering RNA to human dendritic cells to suppress dengue virus infection and associated proinflammatory cytokine production.J. Virol.20108452490250110.1128/JVI.02105‑08 20015996
    [Google Scholar]
  181. AzumaM. RitprajakP. HashiguchiM. Topical application of siRNA targeting cutaneous dendritic cells in allergic skin disease.Methods Mol. Biol.201062337338110.1007/978‑1‑60761‑588‑0_24
    [Google Scholar]
  182. UllahA. RazzaqA. AlfaifiM.Y. Sanguinarine attenuates lung cancer progression via oxidative stress-induced cell apoptosis.Curr. Mol. Pharmacol.202417e1876142926938310.2174/0118761429269383231119062233 38389415
    [Google Scholar]
  183. SinghP. SinghM. SinghB. Implications of siRNA therapy in bone health: Silencing communicates.Biomedicines20241219010.3390/biomedicines12010090 38255196
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240303370240530120450
Loading
/content/journals/cmm/10.2174/0115665240303370240530120450
Loading

Data & Media loading...

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