Skip to content
2000
Volume 32, Issue 24
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Cancer therapy has seen significant advancements in recent years, with the emergence of RNA interference (RNAi) as a promising strategy for targeted gene silencing. However, the successful delivery of small interfering RNA (siRNA) to cancer cells remains a challenge. Chitosan nanoparticles (CSNPs) can be derived from the natural polysaccharide chitin sources. CSNPs have gained considerable attention as a potential solution to encapsulate siRNA due to their biocompatibility, and biodegradability. This article explores the application of CSNPs for siRNA delivery in cancer therapy. Firstly, it discusses the significance of siRNA in gene regulation and highlights its potential to selectively silence oncogenes or tumor suppressor genes, making it a powerful tool in cancer treatment. The obstacles associated with effective siRNA delivery, such as degradation by nucleases and poor cellular uptake, are also addressed. Next, the focus shifts to the unique properties of CSNPs that make them attractive for siRNA delivery. The discussion revolves around how chitosan can interact electrostatically with siRNA to create stable complexes, as well as the controlled release of siRNA from CSNPs. This controlled release ensures sustained and efficient delivery of siRNA to cancer cells, maximizing therapeutic efficacy. Moreover, the biocompatibility and biodegradability of CSNPs make them ideal for applications. Different approaches to modifying and functionalizing surfaces are investigated by emphasizing on enhancement of stability and targeting abilities of CSNPs in cancer treatment. Registered trials for CS and siRNA are summarized, along with ongoing investigations into various applications of chitosan in medical treatments. Overall, the application of CSNPs in siRNA delivery for cancer therapy holds great promise and offers a potential solution to overcome the challenges associated with RNAi-based treatments. Continued advancements in this field will likely lead to improved targeted therapies with reduced side effects, ultimately benefitting cancer patients worldwide.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673286052240426044945
2024-06-05
2025-10-22

  • From This Site

    /content/journals/cmc/10.2174/0109298673286052240426044945
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. GoutasD. PergarisA. GiaginisC. TheocharisS. HuR as therapeutic target in cancer: What the future holds.Curr. Med. Chem.2022291566510.2174/092986732866621062814343034182901
     [Google Scholar]
  2. ArrigoniR. BalliniA. SantacroceL. CantoreS. InchingoloA. InchingoloF. Di DomenicoM. QuagliuoloL. BoccellinoM. Another look at dietary polyphenols: Challenges in cancer prevention and treatment.Curr. Med. Chem.20222961061108210.2174/1875533XMTE3kMjUp234375181
     [Google Scholar]
  3. OzkanE. Bakar-AtesF. Ferroptosis: A trusted ally in combating drug resistance in cancer.Curr. Med. Chem.2022291415510.2174/092986732866621081011581234375173
     [Google Scholar]
  4. SadeghiM. A highly sensitive nanobiosensor based on aptamer-conjugated graphene-decorated rhodium nanoparticles for detection of HER2-positive circulating tumor cells.Nanotechnol. Rev.202211179381010.1515/ntrev‑2022‑0047
     [Google Scholar]
  5. Gooneh-FarahaniS. NaghibS.M. Naimi-JamalM.R. SeyfooriA. A pH-sensitive nanocarrier based on BSA-stabilized graphene-chitosan nanocomposite for sustained and prolonged release of anticancer agents.Sci. Rep.20211111740410.1038/s41598‑021‑97081‑134465842
     [Google Scholar]
  6. 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]
  7. HosseiniS.S. Crocin suppresses colorectal cancer cell proliferation by regulating miR-143/145 and KRAS/RREB1 pathways.Anticancer Agents Med. Chem.2023231719161923
     [Google Scholar]
  8. UllahA. Molecular mechanisms of Sanguinarine in cancer prevention and treatment.Anticancer Agents Med. Chem.202323776577810.2174/1871520622666220831124321
     [Google Scholar]
  9. RahimzadehZ. A rapid nanobiosensing platform based on herceptin-conjugated graphene for ultrasensitive detection of circulating tumor cells in early breast cancer.Nanotechnol. Rev.202110174475310.1515/ntrev‑2021‑0049
     [Google Scholar]
  10. GharehdaghiZ. RahimiR. NaghibS.M. MolaabasiF. Cu (II)-porphyrin metal–organic framework/graphene oxide: synthesis, characterization, and application as a pH-responsive drug carrier for breast cancer treatment.J. Biol. Inorg. Chem.202126668970410.1007/s00775‑021‑01887‑334420089
     [Google Scholar]
  11. ArdevinesS. Marqués-LópezE. HerreraR.P. Heterocycles in breast cancer treatment: The use of pyrazole derivatives.Curr. Med. Chem.202330101145117410.2174/092986732966622082909183036043746
     [Google Scholar]
  12. YounisN.K. YassineH.M. EidA.H. Nanomedicine for cancer.Curr. Med. Chem.202330232592259410.2174/092986733066622122812194736579388
     [Google Scholar]
  13. TangZ. TanY. ChenH. WanY. Benzoxazine: A privileged scaffold in medicinal chemistry.Curr. Med. Chem.202330437238910.2174/092986732966622070514084635792127
     [Google Scholar]
  14. YaghoubiF. MotlaghN.S.H. NaghibS.M. HaghiralsadatF. JalianiH.Z. MoradiA. A functionalized graphene oxide with improved cytocompatibility for stimuli-responsive co-delivery of curcumin and doxorubicin in cancer treatment.Sci. Rep.2022121195910.1038/s41598‑022‑05793‑935121783
     [Google Scholar]
  15. GrossoR. de-PazM.V. Thiolated-polymer-based nanoparticles as an avant-garde approach for anticancer therapies-reviewing thiomers from chitosan and hyaluronic acid.Pharmaceutics202113685410.3390/pharmaceutics1306085434201403
     [Google Scholar]
  16. BaughmanJ. BradshawJ.E. The creation of a next-generation cancer treatment using photodynamic therapy.Honors Theses2021908
     [Google Scholar]
  17. ShahbaziN. Zare-DorabeiR. NaghibS.M. Multifunctional nanoparticles as optical biosensing probe for breast cancer detection: A review.Mater. Sci. Eng. C202112711224910.1016/j.msec.2021.11224934225888
     [Google Scholar]
  18. Pérez-HerreroE. Fernández-MedardeA. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.Eur. J. Pharm. Biopharm.201593527910.1016/j.ejpb.2015.03.01825813885
     [Google Scholar]
  19. AnguelaX.M. HighK.A. Entering the modern era of gene therapy.Annu. Rev. Med.201970127328810.1146/annurev‑med‑012017‑04333230477394
     [Google Scholar]
  20. SenG.L. BlauH.M. A brief history of RNAi: The silence of the genes.FASEB J.20062091293129910.1096/fj.06‑6014rev16816104
     [Google Scholar]
  21. IwasakiS. TomariY. Reconstitution of RNA interference machinery. Argonaute proteins: Methods and protocols.Methods Mol. Biol.2018168013114310.1007/978‑1‑4939‑7339‑2_9
     [Google Scholar]
  22. BeyerS. FlemingJ. MengW. SinghR. HaqueS. ChakravartiA. The role of miRNAs in angiogenesis, invasion and metabolism and their therapeutic implications in gliomas.Cancers2017978510.3390/cancers907008528698530
     [Google Scholar]
  23. Daldrup-LinkH.E. Ten things you might not know about iron oxide nanoparticles.Radiology2017284361662910.1148/radiol.201716275928825888
     [Google Scholar]
  24. HeineA. JuranekS. BrossartP. Clinical and immunological effects of mRNA vaccines in malignant diseases.Mol. Cancer20212015210.1186/s12943‑021‑01339‑133722265
     [Google Scholar]
  25. SahinU. MuikA. DerhovanessianE. VoglerI. KranzL.M. VormehrM. BaumA. PascalK. QuandtJ. MaurusD. BrachtendorfS. LörksV. SikorskiJ. HilkerR. BeckerD. EllerA.K. GrütznerJ. BoeslerC. RosenbaumC. KühnleM.C. LuxemburgerU. Kemmer-BrückA. LangerD. BexonM. BolteS. KarikóK. PalancheT. FischerB. SchultzA. ShiP.Y. Fontes-GarfiasC. PerezJ.L. SwansonK.A. LoschkoJ. ScullyI.L. CutlerM. KalinaW. KyratsousC.A. CooperD. DormitzerP.R. JansenK.U. TüreciÖ. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.Nature2020586783059459910.1038/s41586‑020‑2814‑732998157
     [Google Scholar]
  26. ClementeB. DenisM. SilveiraC.P. SchiavettiF. BrazzoliM. StrangesD. Straight to the point: Targeted mRNA-delivery to immune cells for improved vaccine design.Front. Immunol.202314129492910.3389/fimmu.2023.129492938090568
     [Google Scholar]
  27. JuradoA.R. TanD. JiaoX. KiledjianM. TongL. Structure and function of pre-mRNA 5′-end capping quality control and 3′-end processing.Biochemistry201453121882189810.1021/bi401715v24617759
     [Google Scholar]
  28. DvingeH. KimE. Abdel-WahabO. BradleyR.K. RNA splicing factors as oncoproteins and tumour suppressors.Nat. Rev. Cancer201616741343010.1038/nrc.2016.5127282250
     [Google Scholar]
  29. PengQ. ZhouY. OyangL. WuN. TangY. SuM. LuoX. WangY. ShengX. MaJ. LiaoQ. Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics.Mol. Ther.20223031018103510.1016/j.ymthe.2021.11.01034793975
     [Google Scholar]
  30. DouZ. LeiH. SuW. ZhangT. ChenX. YuB. ZhenX. SiJ. SunC. ZhangH. DiC. Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.Cell Death Dis.202415216010.1038/s41419‑024‑06507‑x38383492
     [Google Scholar]
  31. TaylorD.W. MaE. ShigematsuH. CianfroccoM.A. NolandC.L. NagayamaK. NogalesE. DoudnaJ.A. WangH.W. Substrate-specific structural rearrangements of human Dicer.Nat. Struct. Mol. Biol.201320666267010.1038/nsmb.256423624860
     [Google Scholar]
  32. LuoZ. HuangY. BatraN. ChenY. HuangH. WangY. ZhangZ. LiS. ChenC.Y. WangZ. SunJ. WangQ.J. YangD. LuB. ConwayJ.F. LiL.Y. YuA.M. LiS. Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy.Nat. Commun.202415125510.1038/s41467‑023‑44572‑638177179
     [Google Scholar]
  33. PengY. CroceC.M. The role of MicroRNAs in human cancer.Signal Transduct. Target. Ther.2016111500410.1038/sigtrans.2015.429263891
     [Google Scholar]
  34. AlswailemR. AlqahtaniF.Y. AleanizyF.S. AlrfaeiB.M. BadranM. AlqahtaniQ.H. AbdelhadyH.G. AlsarraI. MicroRNA-219 loaded chitosan nanoparticles for treatment of glioblastoma.Artif. Cells Nanomed. Biotechnol.202250119820710.1080/21691401.2022.209212335762105
     [Google Scholar]
  35. StatelloL. GuoC.J. ChenL.L. HuarteM. Gene regulation by long non-coding RNAs and its biological functions.Nat. Rev. Mol. Cell Biol.20212229611810.1038/s41580‑020‑00315‑933353982
     [Google Scholar]
  36. ArunG. DiermeierS. AkermanM. ChangK.C. WilkinsonJ.E. HearnS. KimY. MacLeodA.R. KrainerA.R. NortonL. BrogiE. EgebladM. SpectorD.L. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.Genes Dev.2016301345110.1101/gad.270959.11526701265
     [Google Scholar]
  37. ZareK. ShademanM. Ghahramani SenoM.M. DehghaniH. CRISPR/Cas9 knockout strategies to ablate CCAT1 lncRNA gene in cancer cells.Biol. Proced. Online20182012110.1186/s12575‑018‑0086‑530410426
     [Google Scholar]
  38. EndoH. ShirokiT. NakagawaT. YokoyamaM. TamaiK. YamanamiH. FujiyaT. SatoI. YamaguchiK. TanakaN. IijimaK. ShimosegawaT. SugamuraK. SatohK. Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer.PLoS One2013810e7707010.1371/journal.pone.007707024130837
     [Google Scholar]
  39. LatgéG. PouletC. BoursV. JosseC. JerusalemG. Natural antisense transcripts: Molecular mechanisms and implications in breast cancers.Int. J. Mol. Sci.201819112310.3390/ijms1901012329301303
     [Google Scholar]
  40. DamiatiL.A. El-MesseiryS. An overview of RNA-based scaffolds for osteogenesis.Front. Mol. Biosci.2021868258110.3389/fmolb.2021.68258134169095
     [Google Scholar]
  41. NingQ. LiuY.F. YeP.J. GaoP. LiZ.P. TangS.Y. HeD.X. TangS.S. WeiH. YuC.Y. Delivery of liver-specific miRNA-122 using a targeted macromolecular prodrug toward synergistic therapy for hepatocellular carcinoma.ACS Appl. Mater. Interfaces20191111105781058810.1021/acsami.9b0063430802029
     [Google Scholar]
  42. El-SayK.M. El-SawyH.S. Polymeric nanoparticles: Promising platform for drug delivery.Int. J. Pharm.20175281-267569110.1016/j.ijpharm.2017.06.05228629982
     [Google Scholar]
  43. PillaiC.K.S. PaulW. SharmaC.P. Chitin and chitosan polymers: Chemistry, solubility and fiber formation.Prog. Polym. Sci.200934764167810.1016/j.progpolymsci.2009.04.001
     [Google Scholar]
  44. DonatoN.R. Obtaining chitosan sulfate and its application in the coagulation-flocculation process of anionic colloidal suspensions of kaolinite.Ibero-American Polymer Magazine200673145161
     [Google Scholar]
  45. XuY. GallertC. WinterJ. Chitin purification from shrimp wastes by microbial deproteination and decalcification.Appl. Microbiol. Biotechnol.200879468769710.1007/s00253‑008‑1471‑918418590
     [Google Scholar]
  46. PhilibertT. LeeB.H. FabienN. Current status and new perspectives on chitin and chitosan as functional biopolymers.Appl. Biochem. Biotechnol.201718141314133710.1007/s12010‑016‑2286‑227787767
     [Google Scholar]
  47. ArbiaW. Chitin extraction from crustacean shells using biological methods–a review.Food Technol. Biotechnol.20135111225
     [Google Scholar]
  48. BhaskarN. SureshP.V. SakhareP.Z. SachindraN.M. Shrimp biowaste fermentation with Pediococcus acidolactici CFR2182: Optimization of fermentation conditions by response surface methodology and effect of optimized conditions on deproteination/demineralization and carotenoid recovery.Enzyme Microb. Technol.20074051427143410.1016/j.enzmictec.2006.10.019
     [Google Scholar]
  49. SagheerF.A.A. Al-SughayerM.A. MuslimS. ElsabeeM.Z. Extraction and characterization of chitin and chitosan from marine sources in Arabian Gulf.Carbohydr. Polym.200977241041910.1016/j.carbpol.2009.01.032
     [Google Scholar]
  50. RinaudoM. Chitin and chitosan: Properties and applications.Prog. Polym. Sci.200631760363210.1016/j.progpolymsci.2006.06.001
     [Google Scholar]
  51. ZhangX. DingC. LiuH. LiuL. ZhaoC. Protective effects of ion-imprinted chitooligosaccharides as uranium-specific chelating agents against the cytotoxicity of depleted uranium in human kidney cells.Toxicology20112861-3758410.1016/j.tox.2011.05.01121645583
     [Google Scholar]
  52. LinY. WangH. GoharF. UllahM.H. ZhangX. XieD. FangH. HuangJ. YangJ. Preparation and copper ions adsorption properties of thiosemicarbazide chitosan from squid pens.Int. J. Biol. Macromol.20179547648310.1016/j.ijbiomac.2016.11.08527889339
     [Google Scholar]
  53. ThambiliyagodageC. JayanettiM. MendisA. EkanayakeG. LiyanaarachchiH. VigneswaranS. Recent advances in chitosan-based applications-a review.Materials2023165207310.3390/ma1605207336903188
     [Google Scholar]
  54. MohammedM. SyedaJ. WasanK. WasanE. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery.Pharmaceutics2017945310.3390/pharmaceutics904005329156634
     [Google Scholar]
  55. GhadiA. MahjoubS. TabandehF. TalebniaF. Synthesis and optimization of chitosan nanoparticles: Potential applications in nanomedicine and biomedical engineering.Caspian J. Intern. Med.20145315616125202443
     [Google Scholar]
  56. WangX. LiJ. WangY. ChoK.J. KimG. GjyreziA. KoenigL. GiannakakouP. ShinH.J.C. TighiouartM. NieS. ChenZ.G. ShinD.M. HFT-T, a targeting nanoparticle, enhances specific delivery of paclitaxel to folate receptor-positive tumors.ACS Nano20093103165317410.1021/nn900649v19761191
     [Google Scholar]
  57. VauthierC. ZandanelC. RamonA.L. Chitosan-based nanoparticles for in vivo delivery of interfering agents including siRNA.Curr. Opin. Colloid Interface Sci.201318540641810.1016/j.cocis.2013.06.005
     [Google Scholar]
  58. McKiernanP.J. CunninghamO. GreeneC.M. CryanS.A. Targeting miRNA-based medicines to cystic fibrosis airway epithelial cells using nanotechnology.Int. J. Nanomedicine201383907391524143095
     [Google Scholar]
  59. RagelleH. VandermeulenG. PréatV. Chitosan-based siRNA delivery systems.J. Control. Release2013172120721810.1016/j.jconrel.2013.08.00523965281
     [Google Scholar]
  60. HowardK.A. RahbekU.L. LiuX. DamgaardC.K. GludS.Z. AndersenM.Ø. HovgaardM.B. SchmitzA. NyengaardJ.R. BesenbacherF. KjemsJ. RNA interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system.Mol. Ther.200614447648410.1016/j.ymthe.2006.04.01016829204
     [Google Scholar]
  61. KongF. LiuG. SunB. ZhouS. ZuoA. ZhaoR. LiangD. Phosphorylatable short peptide conjugated low molecular weight chitosan for efficient siRNA delivery and target gene silencing.Int. J. Pharm.20124221-244545310.1016/j.ijpharm.2011.10.04122067703
     [Google Scholar]
  62. KatasH. AlparH.O. Development and characterisation of chitosan nanoparticles for siRNA delivery.J. Control. Release2006115221622510.1016/j.jconrel.2006.07.02116959358
     [Google Scholar]
  63. RaviñaM. CubilloE. OlmedaD. Novoa-CarballalR. Fernandez-MegiaE. RigueraR. SánchezA. CanoA. AlonsoM.J. Hyaluronic acid/chitosan-g-poly(ethylene glycol) nanoparticles for gene therapy: An application for pDNA and siRNA delivery.Pharm. Res.201027122544255510.1007/s11095‑010‑0263‑y20857179
     [Google Scholar]
  64. Al-AbsiM.Y. CaprificoA.E. CalabreseG. Chitosan and its structural modifications for siRNA delivery.Adv. Pharm. Bull.202313227528210.34172/apb.2023.03037342385
     [Google Scholar]
  65. ChaJ.H. ChanL.C. LiC.W. HsuJ.L. HungM.C. Mechanisms controlling PD-L1 expression in cancer.Mol. Cell201976335937010.1016/j.molcel.2019.09.03031668929
     [Google Scholar]
  66. LiC. HanX. Melanoma cancer immunotherapy using PD-L1 siRNA and imatinib promotes cancer-immunity cycle.Pharm. Res.202037610910.1007/s11095‑020‑02838‑432476052
     [Google Scholar]
  67. XueT. WangL. LiY. SongH. ChuH. YangH. GuoA. JiaoJ. SiRNA-mediated RRM2 gene silencing combined with cisplatin in the treatment of epithelial ovarian cancer in vivo: An experimental study of nude mice.Int. J. Med. Sci.201916111510151610.7150/ijms.3397931673243
     [Google Scholar]
  68. ZhangQ. ZhangH. NingT. LiuD. DengT. LiuR. BaiM. ZhuK. LiJ. QianF. YingG. BaY. Exosome-delivered c-Met siRNA could reverse chemoresistance to cisplatin in gastric cancer.Int. J. Nanomedicine2020152323233510.2147/IJN.S23121432308384
     [Google Scholar]
  69. AnilmisN.M. KaraG. KilicayE. HazerB. DenkbasE.B. Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy.J. Microencapsul.201936763564810.1080/02652048.2019.166511731509450
     [Google Scholar]
  70. JiangX. Chitosan-g-PEG/DNA complexes deliver gene to the rat liver via intrabiliary and intraportal infusions.J. Gene. Med.200684477487
     [Google Scholar]
  71. PingY. LiuC. ZhangZ. LiuK.L. ChenJ. LiJ. Chitosan-graft-(PEI-β-cyclodextrin) copolymers and their supramolecular PEGylation for DNA and siRNA delivery.Biomaterials201132328328834110.1016/j.biomaterials.2011.07.03821840593
     [Google Scholar]
  72. FischerD. OsburgB. PetersenH. KisselT. BickelU. Effect of poly(ethylene imine) molecular weight and pegylation on organ distribution and pharmacokinetics of polyplexes with oligodeoxynucleotides in mice.Drug Metab. Dispos.200432998399215319340
     [Google Scholar]
  73. LeeH. JeongJ.H. ParkT.G. PEG grafted polylysine with fusogenic peptide for gene delivery: high transfection efficiency with low cytotoxicity.J. Control. Release2002791-328329110.1016/S0168‑3659(02)00002‑011853938
     [Google Scholar]
  74. ShaliH. ShabaniM. PourgholiF. HajivaliliM. Aghebati-MalekiL. Jadidi-NiaraghF. BaradaranB. Movassaghpour AkbariA.A. YounesiV. YousefiM. Co-delivery of insulin-like growth factor 1 receptor specific siRNA and doxorubicin using chitosan-based nanoparticles enhanced anticancer efficacy in A549 lung cancer cell line.Artif. Cells Nanomed. Biotechnol.201846229330210.1080/21691401.2017.130721228362176
     [Google Scholar]
  75. BraeckmansK. BuyensK. BouquetW. VervaetC. JoyeP. VosF.D. PlawinskiL. DoeuvreL. Angles- CanoE. SandersN.N. DemeesterJ. SmedtS.C.D. Sizing nanomatter in biological fluids by fluorescence single particle tracking.Nano Lett.201010114435444210.1021/nl103264u20923181
     [Google Scholar]
  76. BuyensK. MeyerM. WagnerE. DemeesterJ. De SmedtS.C. SandersN.N. Monitoring the disassembly of siRNA polyplexes in serum is crucial for predicting their biological efficacy.J. Control. Release20101411384110.1016/j.jconrel.2009.08.02619737587
     [Google Scholar]
  77. MorrisseyD.V. LockridgeJ.A. ShawL. BlanchardK. JensenK. BreenW. HartsoughK. MachemerL. RadkaS. JadhavV. VaishN. ZinnenS. VargeeseC. BowmanK. ShafferC.S. JeffsL.B. JudgeA. MacLachlanI. PoliskyB. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs.Nat. Biotechnol.20052381002100710.1038/nbt112216041363
     [Google Scholar]
  78. GaoY. ZhangZ. ChenL. GuW. LiY. Chitosan N- betainates/DNA self-assembly nanoparticles for gene delivery: In vitro uptake and transfection efficiency.Int. J. Pharm.20093711-215616210.1016/j.ijpharm.2008.12.01219135139
     [Google Scholar]
  79. SharmaK. SomavarapuS. ColombaniA. GovindN. TaylorK.M.G. Nebulised siRNA encapsulated crosslinked chitosan nanoparticles for pulmonary delivery.Int. J. Pharm.20134551-224124710.1016/j.ijpharm.2013.07.02423876499
     [Google Scholar]
  80. ZhangY. ChenJ. ZhangY. PanY. ZhaoJ. RenL. LiaoM. HuZ. KongL. WangJ. A novel PEGylation of chitosan nanoparticles for gene delivery.Biotechnol. Appl. Biochem.200746419720410.1042/BA2006016317147512
     [Google Scholar]
  81. NimeshS. ThibaultM.M. LavertuM. BuschmannM.D. Enhanced gene delivery mediated by low molecular weight chitosan/DNA complexes: Effect of pH and serum.Mol. Biotechnol.201046218219610.1007/s12033‑010‑9286‑120454872
     [Google Scholar]
  82. YueZ.G. WeiW. LvP.P. YueH. WangL.Y. SuZ.G. MaG.H. Surface charge affects cellular uptake and intracellular trafficking of chitosan-based nanoparticles.Biomacromolecules20111272440244610.1021/bm101482r21657799
     [Google Scholar]
  83. BuschmannM.D. MerzoukiA. LavertuM. ThibaultM. JeanM. DarrasV. Chitosans for delivery of nucleic acids.Adv. Drug Deliv. Rev.20136591234127010.1016/j.addr.2013.07.00523872012
     [Google Scholar]
  84. MaoS. SunW. KisselT. Chitosan-based formulations for delivery of DNA and siRNA.Adv. Drug Deliv. Rev.2010621122710.1016/j.addr.2009.08.00419796660
     [Google Scholar]
  85. MalhotraM. Tomaro-DuchesneauC. PrakashS. Synthesis of TAT peptide-tagged PEGylated chitosan nanoparticles for siRNA delivery targeting neurodegenerative diseases.Biomaterials20133441270128010.1016/j.biomaterials.2012.10.01323140978
     [Google Scholar]
  86. LiW. NicolF. SzokaF.C.Jr GALA: A designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery.Adv. Drug Deliv. Rev.200456796798510.1016/j.addr.2003.10.04115066755
     [Google Scholar]
  87. MaZ. YangC. SongW. WangQ. KjemsJ. GaoS. Chitosan Hydrogel as siRNA vector for prolonged gene silencing.J. Nanobiotechnology20141212310.1186/1477‑3155‑12‑2324946934
     [Google Scholar]
  88. RaperS.E. ChirmuleN. LeeF.S. WivelN.A. BaggA. GaoG. WilsonJ.M. BatshawM.L. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer.Mol. Genet. Metab.2003801-214815810.1016/j.ymgme.2003.08.01614567964
     [Google Scholar]
  89. SongW. SongX. YangC. GaoS. KlausenL.H. ZhangY. DongM. KjemsJ. Chitosan/siRNA functionalized titanium surface via a layer-by-layer approach for in vitro sustained gene silencing and osteogenic promotion.Int. J. Nanomedicine2015102335234625848254
     [Google Scholar]
  90. CaoY. TanY.F. WongY.S. AminuddinM. RamyaB. LiewM.W.J. LiuJ. VenkatramanS.S. Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects.Sci. Rep.2022121352710.1038/s41598‑022‑07554‑035241750
     [Google Scholar]
  91. ChangW.W. LinR.J. YuJ. ChangW.Y. FuC.H. LaiA.C.Y. YuJ.C. YuA.L. The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitors.Breast Cancer Res.2013153R3910.1186/bcr342323663564
     [Google Scholar]
  92. JafariR. Majidi ZolbaninN. MajidiJ. AtyabiF. YousefiM. Jadidi-NiaraghF. Aghebati-MalekiL. ShanehbandiD. Soltani ZangbarM.S. RafatpanahH. Anti-mucin1 aptamer-conjugated chitosan nanoparticles for targeted co-delivery of docetaxel and IGF-1R siRNA to SKBR3 metastatic breast cancer cells.Iran. Biomed. J.2019231213310.29252/ibj.23.1.2130041514
     [Google Scholar]
  93. MasjediA. AhmadiA. AtyabiF. FarhadiS. IrandoustM. Khazaei-PoulY. Ghasemi ChaleshtariM. Edalati FathabadM. BaghaeiM. HaghnavazN. BaradaranB. Hojjat-FarsangiM. GhalamfarsaG. SabzG. HasanzadehS. Jadidi-NiaraghF. Silencing of IL-6 and STAT3 by siRNA loaded hyaluronate-N,N,N-trimethyl chitosan nanoparticles potently reduces cancer cell progression.Int. J. Biol. Macromol.202014948750010.1016/j.ijbiomac.2020.01.27332004600
     [Google Scholar]
  94. AshrafizadehM. ZarrabiA. HushmandiK. HashemiF. Rahmani MoghadamE. RaeiM. KalantariM. TavakolS. MohammadinejadR. NajafiM. TayF.R. MakvandiP. Progress in natural compounds/sirna co-delivery employing nanovehicles for cancer therapy.ACS Comb. Sci.2020221266970010.1021/acscombsci.0c0009933095554
     [Google Scholar]
  95. PourmadadiM. AbbasiP. EshaghiM.M. BakhshiA. Ezra ManicumA-L. RahdarA. PandeyS. JadounS. Díez-PascualA.M. Curcumin delivery and co-delivery based on nanomaterials as an effective approach for cancer therapy.J. Drug Deliv. Sci. Technol.20227810398210.1016/j.jddst.2022.103982
     [Google Scholar]
  96. ChenW. LiuZ. MaiW. XiaoY. YouX. QinL. FZD8 indicates a poor prognosis and promotes gastric cancer invasion and metastasis via B-catenin signaling pathway.Ann. Clin. Lab. Sci.2020501132332161008
     [Google Scholar]
  97. RudzinskiW.E. PalaciosA. AhmedA. LaneM.A. AminabhaviT.M. Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles.Carbohydr. Polym.201614732333210.1016/j.carbpol.2016.04.04127178938
     [Google Scholar]
  98. LeeJ.H. MohanC.D. DeivasigamaniA. JungY.Y. RangappaS. BasappaS. ChinnathambiA. AlahmadiT.A. AlharbiS.A. GargM. LinZ.X. RangappaK.S. SethiG. HuiK.M. AhnK.S. Brusatol suppresses STAT3-driven metastasis by downregulating epithelial-mesenchymal transition in hepatocellular carcinoma.J. Adv. Res.202026839410.1016/j.jare.2020.07.00433133685
     [Google Scholar]
  99. YangM.H. BaekS.H. ChinnathambiA. AlharbiS.A. AhnK.S. Identification of protocatechuic acid as a novel blocker of epithelial-to-mesenchymal transition in lung tumor cells.Phytother. Res.20213541953196610.1002/ptr.693833251669
     [Google Scholar]
  100. AfkhamA. Aghebati-MalekiL. SiahmansouriH. SadreddiniS. AhmadiM. DolatiS. AfkhamN.M. AkbarzadehP. Jadidi-NiaraghF. YounesiV. YousefiM. Chitosan (CMD)-mediated co-delivery of SN38 and Snail-specific siRNA as a useful anticancer approach against prostate cancer.Pharmacol. Rep.201870341842510.1016/j.pharep.2017.11.00529626645
     [Google Scholar]
  101. DengZ.J. MortonS.W. BonnerD.K. GuL. OwH. HammondP.T. A plug-and-play ratiometric pH-sensing nanoprobe for high-throughput investigation of endosomal escape.Biomaterials20155125025610.1016/j.biomaterials.2015.02.01325771015
     [Google Scholar]
  102. FerreiraC.S.M. MatthewsC.S. MissailidisS. DNA aptamers that bind to MUC1 tumour marker: Design and characterization of MUC1-binding single-stranded DNA aptamers.Tumour Biol.200627628930110.1159/00009608517033199
     [Google Scholar]
  103. DaviesH. BignellG.R. CoxC. StephensP. EdkinsS. CleggS. TeagueJ. WoffendinH. GarnettM.J. BottomleyW. DavisN. DicksE. EwingR. FloydY. GrayK. HallS. HawesR. HughesJ. KosmidouV. MenziesA. MouldC. ParkerA. StevensC. WattS. HooperS. WilsonR. JayatilakeH. GustersonB.A. CooperC. ShipleyJ. HargraveD. Pritchard-JonesK. MaitlandN. Chenevix-TrenchG. RigginsG.J. BignerD.D. PalmieriG. CossuA. FlanaganA. NicholsonA. HoJ.W.C. LeungS.Y. YuenS.T. WeberB.L. SeiglerH.F. DarrowT.L. PatersonH. MaraisR. MarshallC.J. WoosterR. StrattonM.R. FutrealP.A. Mutations of the BRAF gene in human cancer.Nature2002417689294995410.1038/nature0076612068308
     [Google Scholar]
  104. WellbrockC. RanaS. PatersonH. PickersgillH. BrummelkampT. MaraisR. Oncogenic BRAF regulates melanoma proliferation through the lineage specific factor MITF.PLoS One200837e273410.1371/journal.pone.000273418628967
     [Google Scholar]
  105. HugdahlE. KalvenesM.B. PuntervollH.E. LadsteinR.G. AkslenL.A. BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival.Br. J. Cancer2016114780180810.1038/bjc.2016.4426924424
     [Google Scholar]
  106. LukeJ.J. FlahertyK.T. RibasA. LongG.V. Targeted agents and immunotherapies: Optimizing outcomes in melanoma.Nat. Rev. Clin. Oncol.201714846348210.1038/nrclinonc.2017.4328374786
     [Google Scholar]
  107. HuoJ. Effects of chitosan nanoparticle-mediated BRAF siRNA interference on invasion and metastasis of gastric cancer cells.Artif. Cells Nanomed. Biotechnol.20164451232123510.3109/21691401.2015.101966625794798
     [Google Scholar]
  108. BasergaR. PeruzziF. ReissK. The IGF-1 receptor in cancer biology.Int. J. Cancer2003107687387710.1002/ijc.1148714601044
     [Google Scholar]
  109. BanerjeeK. ResatH. Constitutive activation of STAT 3 in breast cancer cells: A review.Int. J. Cancer2016138112570257810.1002/ijc.2992326559373
     [Google Scholar]
  110. SubramaniR. Lopez-ValdezR. ArumugamA. NandyS. BoopalanT. LakshmanaswamyR. Targeting insulin- like growth factor 1 receptor inhibits pancreatic cancer growth and metastasis.PLoS One201495e9701610.1371/journal.pone.009701624809702
     [Google Scholar]
  111. ZhangH. PelzerA.M. KiangD.T. YeeD. Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin.Cancer Res.200767139139710.1158/0008‑5472.CAN‑06‑171217210722
     [Google Scholar]
  112. MayerI.A. AbramsonV.G. LehmannB.D. PietenpolJ.A. New strategies for triple-negative breast cancer--deciphering the heterogeneity.Clin. Cancer Res.201420478279010.1158/1078‑0432.CCR‑13‑058324536073
     [Google Scholar]
  113. ChenJ. WoD. MaE. YanH. PengJ. ZhuW. FangY. RenD. Deletion of low-density lipoprotein-related receptor 5 inhibits liver Cancer cell proliferation via destabilizing Nucleoporin 37.Cell Commun. Signal.201917117410.1186/s12964‑019‑0495‑331881970
     [Google Scholar]
  114. WangT. RahimizadehK. VeeduR.N. Development of a novel DNA oligonucleotide targeting low-density lipoprotein receptor.Mol. Ther. Nucleic Acids20201919019810.1016/j.omtn.2019.11.00431841991
     [Google Scholar]
  115. YangS.D. ZhuW.J. ZhuQ.L. ChenW.L. RenZ.X. LiF. YuanZ.Q. LiJ.Z. LiuY. ZhouX.F. LiuC. ZhangX.N. Binary-copolymer system base on low-density lipoprotein-coupled N-succinyl chitosan lipoic acid micelles for co-delivery MDR1 siRNA and paclitaxel, enhances antitumor effects via reducing drug.J. Biomed. Mater. Res. B Appl. Biomater.201710551114112510.1002/jbm.b.3363627008163
     [Google Scholar]
  116. PengH. QiaoL. ShanG. GaoM. ZhangR. YiX. HeX. Stepwise responsive carboxymethyl chitosan-based nanoplatform for effective drug-resistant breast cancer suppression.Carbohydr. Polym.202229111955410.1016/j.carbpol.2022.11955435698382
     [Google Scholar]
  117. GuoH. LiuF. YangS. XueT. Emodin alleviates gemcitabine resistance in pancreatic cancer by inhibiting MDR1/P-glycoprotein and MRPs expression.Oncol. Lett.2020205110.3892/ol.2020.1203032934734
     [Google Scholar]
  118. WangZ. LiangY. LiuY. XiaH. LiuJ. JinX. LiZ. The pH-triggered polyglutamate brush co-delivery of MDR1 and survivin-targeting siRNAs efficiently overcomes multi-drug resistance of NSCLC.Drug Dev. Ind. Pharm.202046111862187210.1080/03639045.2020.182286032924641
     [Google Scholar]
  119. YheeJ.Y. SongS. LeeS.J. ParkS.G. KimK.S. KimM.G. SonS. KooH. KwonI.C. JeongJ.H. JeongS.Y. KimS.H. KimK. Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance.J. Control. Release20151981910.1016/j.jconrel.2014.11.01925481438
     [Google Scholar]
  120. YuS. ChenY. LiX. GaoZ. LiuG. Chitosan nanoparticle-delivered siRNA reduces CXCR4 expression and sensitizes breast cancer cells to cisplatin.Biosci. Rep.2017373BSR2017012210.1042/BSR2017012228446538
     [Google Scholar]
  121. BusilloJ.M. BenovicJ.L. Regulation of CXCR4 signaling.Biochim. Biophys. Acta Biomembr.20071768495296310.1016/j.bbamem.2006.11.002
     [Google Scholar]
  122. SchmidB.C. RudasM. RezniczekG.A. LeodolterS. ZeillingerR. CXCR4 is expressed in ductal carcinoma in situ of the breast and in atypical ductal hyperplasia.Breast Cancer Res. Treat.200484324725010.1023/B:BREA.0000019962.18922.8715026622
     [Google Scholar]
  123. LiS. FanY. KumagaiA. KawakitaE. KitadaM. KanasakiK. KoyaD. Deficiency in dipeptidyl peptidase-4 promotes chemoresistance through the CXCL12/CXCR4/mTOR/TGFβ signaling pathway in breast cancer cells.Int. J. Mol. Sci.202021380510.3390/ijms2103080531991851
     [Google Scholar]
  124. ZhangF. CuiJ. GaoH. YuH. GaoF. ChenJ. ChenL. Cancer-associated fibroblasts induce epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer via CXCL12/CXCR4 axis.Future Oncol.202016322619263310.2217/fon‑2020‑009532804554
     [Google Scholar]
  125. BarbosaJ. NascimentoA.V. FariaJ. SilvaP. BousbaaH. The spindle assembly checkpoint: Perspectives in tumorigenesis and cancer therapy.Front. Biol.20116214715510.1007/s11515‑011‑1122‑x
     [Google Scholar]
  126. KatoT. DaigoY. AragakiM. IshikawaK. SatoM. KondoS. KajiM. Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients.Lung Cancer201174112413110.1016/j.lungcan.2011.01.02521376419
     [Google Scholar]
  127. NascimentoA.V. GattaccecaF. SinghA. BousbaaH. FerreiraD. SarmentoB. AmijiM.M. Biodistribution and pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models.Nanomedicine201611776778110.2217/nnm.16.1426980454
     [Google Scholar]
  128. WuB. YuanY. HanX. WangQ. ShangH. LiangX. JingH. ChengW. Structure of LINC00511-siRNA- conjugated nanobubbles and improvement of cisplatin sensitivity on triple negative breast cancer.FASEB J.20203479713972610.1096/fj.202000481R32497336
     [Google Scholar]
  129. GellertG.C. JacksonS.R. DikmenZ.G. WrightW.E. ShayJ.W. Telomerase as a therapeutic target in cancer.Drug Discov. Today Dis. Mech.20052215916410.1016/j.ddmec.2005.05.009
     [Google Scholar]
  130. WeiW. LvP.P. ChenX.M. YueZ.G. FuQ. LiuS.Y. YueH. MaG.H. Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression.Biomaterials201334153912392310.1016/j.biomaterials.2013.02.03023453062
     [Google Scholar]
  131. MiossecP. KollsJ.K. Targeting IL-17 and TH17 cells in chronic inflammation.Nat. Rev. Drug Discov.2012111076377610.1038/nrd379423023676
     [Google Scholar]
  132. HirotaK. DuarteJ.H. VeldhoenM. HornsbyE. LiY. CuaD.J. AhlforsH. WilhelmC. TolainiM. MenzelU. GarefalakiA. PotocnikA.J. StockingerB. Fate mapping of IL-17-producing T cells in inflammatory responses.Nat. Immunol.201112325526310.1038/ni.199321278737
     [Google Scholar]
  133. DebT.B. ZuoA.H. BarndtR.J. SenguptaS. JankovicR. JohnsonM.D. Pnck overexpression in HER-2 gene-amplified breast cancer causes Trastuzumab resistance through a paradoxical PTEN-mediated process.Breast Cancer Res. Treat.2015150234736110.1007/s10549‑015‑3337‑z25773930
     [Google Scholar]
  134. ReynoldsJ.M. LeeY.H. ShiY. WangX. AngkasekwinaiP. NallaparajuK.C. FlahertyS. ChangS.H. WataraiH. DongC. Interleukin-17B antagonizes interleukin-25-mediated mucosal inflammation.Immunity201542469270310.1016/j.immuni.2015.03.00825888259
     [Google Scholar]
  135. SiahmansouriH. SomiM.H. BabalooZ. BaradaranB. Jadidi-NiaraghF. AtyabiF. MohammadiH. AhmadiM. YousefiM. Effects of HMGA2 siRNA and doxorubicin dual delivery by chitosan nanoparticles on cytotoxicity and gene expression of HT-29 colorectal cancer cell line.J. Pharm. Pharmacol.20166891119113010.1111/jphp.1259327350211
     [Google Scholar]
  136. Seifi-NajmiM. HajivaliliM. SafaralizadehR. SadreddiniS. EsmaeiliS. RazaviR. AhmadiM. MikaeiliH. BaradaranB. Shams-AsenjanK. YousefiM. SiRNA/DOX lodeded chitosan based nanoparticles: Development, characterization and in vitro evaluation on A549 lung cancer cell line.Cell. Mol. Biol.20166211879427755958
     [Google Scholar]
  137. SunP. HuangW. JinM. WangQ. FanB. KangL. GaoZ. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.Int. J. Nanomedicine2016114931494510.2147/IJN.S10542727729789
     [Google Scholar]
  138. LiuX. HowardK.A. DongM. AndersenM.Ø. RahbekU.L. JohnsenM.G. HansenO.C. BesenbacherF. KjemsJ. The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing.Biomaterials20072861280128810.1016/j.biomaterials.2006.11.00417126901
     [Google Scholar]
  139. DehousseV. GarbackiN. JaspartS. CastagneD. PielG. ColigeA. EvrardB. Comparison of chitosan/siRNA and trimethylchitosan/siRNA complexes behaviour in vitro.Int. J. Biol. Macromol.201046334234910.1016/j.ijbiomac.2010.01.01020096725
     [Google Scholar]
  140. UnsoyG. GunduzU. Targeted silencing of Survivin in cancer cells by siRNA loaded chitosan magnetic nanoparticles.Expert Rev. Anticancer Ther.201616778979710.1080/14737140.2016.118498127130312
     [Google Scholar]
  141. ŞalvaE. KabasakalL. ErenF. ÖzkanN. ÇakalağaoğluF. AkbuğaJ. Local delivery of chitosan/VEGF siRNA nanoplexes reduces angiogenesis and growth of breast cancer in vivo.Nucleic Acid Ther.2012221404810.1089/nat.2011.031222217324
     [Google Scholar]
  142. CapelV. VllasaliuD. WattsP. ClarkeP.A. LuxtonD. GrabowskaA.M. MantovaniG. StolnikS. Water- soluble substituted chitosan derivatives as technology platform for inhalation delivery of siRNA.Drug Deliv.201825164465310.1080/10717544.2018.144066829493294
     [Google Scholar]
  143. WangK. KievitF.M. ShamJ.G. JeonM. StephenZ.R. BakthavatsalamA. ParkJ.O. ZhangM. Iron-oxide-based nanovector for tumor targeted siRNA delivery in an orthotopic hepatocellular carcinoma xenograft mouse model.Small201612447748710.1002/smll.20150198526641029
     [Google Scholar]
  144. WuD. MaZ. MaD. LiQ. Long non-coding RNA maternally expressed gene 3 affects cell proliferation, apoptosis and migration by targeting the microRNA-9-5p/midkine axis and activating the phosphoinositide-dependent kinase/AKT pathway in hepatocellular carcinoma.Oncol. Lett.202121534510.3892/ol.2021.1260633747202
     [Google Scholar]
  145. BieC. Insulin-like growth factor 1 receptor drives hepatocellular carcinoma growth and invasion by activating Stat3-midkine-Stat3 loop.Dig. Dis. Sci.202111633559791
     [Google Scholar]
  146. ZhongJ. HuangH.L. LiJ. QianF.C. LiL.Q. NiuP.P. DaiL.C. Development of hybrid-type modified chitosan derivative nanoparticles for the intracellular delivery of midkine-siRNA in hepatocellular carcinoma cells.Hepatobiliary Pancreat. Dis. Int.2015141828910.1016/S1499‑3872(15)60336‑825655295
     [Google Scholar]
  147. TuJ. ZhaoZ. XuM. ChenM. WengQ. JiJ. LINC00460 promotes hepatocellular carcinoma development through sponging miR-485-5p to up-regulate PAK1.Biomed. Pharmacother.201911810921310.1016/j.biopha.2019.10921331376654
     [Google Scholar]
  148. IyerS.C. GopalA. HalagowderD. Myricetin induces apoptosis by inhibiting P21 activated kinase 1 (PAK1) signaling cascade in hepatocellular carcinoma.Mol. Cell. Biochem.20154071-222323710.1007/s11010‑015‑2471‑626104578
     [Google Scholar]
  149. WongL.L.Y. LamI.P.Y. WongT.Y.N. LaiW.L. LiuH.F. YeungL.L. ChingY.P. IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation.PLoS One201387e6884310.1371/journal.pone.006884323894351
     [Google Scholar]
  150. ZhengQ.C. JiangS. WuY.Z. ShangD. ZhangY. HuS.B. ChengX. ZhangC. SunP. GaoY. SongZ.F. LiM. Dual-targeting nanoparticle-mediated gene therapy strategy for hepatocellular carcinoma by delivering small interfering RNA.Front. Bioeng. Biotechnol.2020851210.3389/fbioe.2020.0051232587849
     [Google Scholar]
  151. XuD. WangY. WuJ. ZhangZ. ChenJ. XieM. TangR. ChenC. ChenL. LinS. LuoX. ZhengJ. ECT2 overexpression promotes the polarization of tumor-associated macrophages in hepatocellular carcinoma via the ECT2/PLK1/PTEN pathway.Cell Death Dis.202112216210.1038/s41419‑021‑03450‑z33558466
     [Google Scholar]
  152. ZhangC. WangX. FangD. XuP. MoX. HuC. AbdelattyA. WangM. XuH. SunQ. ZhouG. SheJ. XiaJ. HuiK.M. XiaH. STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway.Theranostics20211152108212210.7150/thno.4811233500714
     [Google Scholar]
  153. LinX.T. YuH.Q. FangL. TanY. LiuZ.Y. WuD. ZhangJ. XiongH.J. XieC.M. Elevated FBXO45 promotes liver tumorigenesis through enhancing IGF2BP1 ubiquitination and subsequent PLK1 upregulation.eLife202110e7071510.7554/eLife.7071534779401
     [Google Scholar]
  154. WangD. Polo-like kinase 1-targeting chitosan nanoparticles suppress the progression of hepatocellular carcinoma.Anticancer Agents Med. Chem.2017177948954
     [Google Scholar]
  155. HanL. TangC. YinC. Enhanced antitumor efficacies of multifunctional nanocomplexes through knocking down the barriers for siRNA delivery.Biomaterials20154411112110.1016/j.biomaterials.2014.12.02025617131
     [Google Scholar]
  156. WuN. Targeting exosomal miRNA with pH-sensitive liposome coated chitosan-siRNA nanoparticles for inhibition of hepatocellular carcinoma metastasis.J Control Release2015213e8210.1016/j.jconrel.2015.05.136
     [Google Scholar]
  157. XuB. XuY. SuG. ZhuH. ZongL. A multifunctional nanoparticle constructed with a detachable albumin outer shell and a redox-sensitive inner core for efficient siRNA delivery to hepatocellular carcinoma cells.J. Drug Target.2018261094195410.1080/1061186X.2018.145584029564911
     [Google Scholar]
  158. DoolittleH. MorelA. TalbotD. Survivin-directed anticancer therapies â a review of pre-clinical data and early-phase clinical trials.Eur. Oncol.201061101410.17925/EOH.2010.06.1.10
     [Google Scholar]
  159. KunduA.K. ChandraP.K. HazariS. PramarY.V. DashS. MandalT.K. Development and optimization of nanosomal formulations for siRNA delivery to the liver.Eur. J. Pharm. Biopharm.201280225726710.1016/j.ejpb.2011.10.02322119665
     [Google Scholar]
  160. KiM.H. KimJ.E. LeeY.N. NohS.M. AnS.W. ChoH.J. KimD.D. Chitosan-based hybrid nanocomplex for siRNA delivery and its application for cancer therapy.Pharm. Res.201431123323333410.1007/s11095‑014‑1422‑324858398
     [Google Scholar]
  161. MartinD.T. SteinbachJ.M. LiuJ. ShimizuS. KaimakliotisH.Z. WheelerM.A. HittelmanA.B. Mark SaltzmanW. WeissR.M. Surface-modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer.Mol. Cancer Ther.2014131718110.1158/1535‑7163.MCT‑13‑050224222663
     [Google Scholar]
  162. MarhabaR. ZöllerM. CD44 in cancer progression: Adhesion, migration and growth regulation.J. Mol. Histol.200335321123110.1023/B:HIJO.0000032354.94213.6915339042
     [Google Scholar]
  163. LiangY. WangY. WangL. LiangZ. LiD. XuX. ChenY. YangX. ZhangH. NiuH. Self-crosslinkable chitosan-hyaluronic acid dialdehyde nanoparticles for CD44-targeted siRNA delivery to treat bladder cancer.Bioact. Mater.20216243344610.1016/j.bioactmat.2020.08.01932995671
     [Google Scholar]
  164. Abdul Ghafoor RajaM. KatasH. Jing WenT. Stability, intracellular delivery, and release of siRNA from chitosan nanoparticles using different cross-linkers.PLoS One2015106e012896310.1371/journal.pone.012896326068222
     [Google Scholar]
  165. LazovicJ. JensenM.C. FerkassianE. AguilarB. RaubitschekA. JacobsR.E. Imaging immune response in vivo: Cytolytic action of genetically altered T cells directed to glioblastoma multiforme.Clin. Cancer Res.200814123832383910.1158/1078‑0432.CCR‑07‑506718559603
     [Google Scholar]
  166. ZhangB.F. XingL. CuiP.F. WangF.Z. XieR.L. ZhangJ.L. ZhangM. HeY.J. LyuJ.Y. QiaoJ.B. ChenB.A. JiangH.L. Mitochondria apoptosis pathway synergistically activated by hierarchical targeted nanoparticles co-delivering siRNA and lonidamine.Biomaterials20156117818910.1016/j.biomaterials.2015.05.02726004233
     [Google Scholar]
  167. LiaoZ.X. HoY.C. ChenH.L. PengS.F. HsiaoC.W. SungH.W. Enhancement of efficiencies of the cellular uptake and gene silencing of chitosan/siRNA complexes via the inclusion of a negatively charged poly(γ-glutamic acid).Biomaterials201031338780878810.1016/j.biomaterials.2010.07.08620800274
     [Google Scholar]
  168. YoonH.Y. SonS. LeeS.J. YouD.G. YheeJ.Y. ParkJ.H. SwierczewskaM. LeeS. KwonI.C. KimS.H. KimK. PomperM.G. Glycol chitosan nanoparticles as specialized cancer therapeutic vehicles: Sequential delivery of doxorubicin and Bcl-2 siRNA.Sci. Rep.201441687810.1038/srep0687825363213
     [Google Scholar]
  169. LeeJ.H. KuS.H. KimM.J. LeeS.J. KimH.C. KimK. KimS.H. KwonI.C. Rolling circle transcription-based polymeric siRNA nanoparticles for tumor-targeted delivery.J. Control. Release2017263293810.1016/j.jconrel.2017.03.39028373128
     [Google Scholar]
  170. GaoY. WangZ.Y. ZhangJ. ZhangY. HuoH. WangT. JiangT. WangS. RVG-peptide-linked trimethylated chitosan for delivery of siRNA to the brain.Biomacromolecules20141531010101810.1021/bm401906p24547943
     [Google Scholar]
  171. HanL. TangC. YinC. Effect of binding affinity for siRNA on the in vivo antitumor efficacy of polyplexes.Biomaterials201334215317532710.1016/j.biomaterials.2013.03.06023591392
     [Google Scholar]
  172. LiY. YangJ. XuB. GaoF. WangW. LiuW. Enhanced therapeutic siRNA to tumor cells by a pH-sensitive agmatine–chitosan bioconjugate.ACS Appl. Mater. Interfaces20157158114812410.1021/acsami.5b0085125832629
     [Google Scholar]
  173. JereD. JiangH.L. KimY.K. AroteR. ChoiY.J. YunC.H. ChoM.H. ChoC.S. Chitosan-graft-polyethylenimine for Akt1 siRNA delivery to lung cancer cells.Int. J. Pharm.20093781-219420010.1016/j.ijpharm.2009.05.04619501140
     [Google Scholar]
  174. ChuN.R. WuH.B. WuT-C. BouxL.J. SiegelM.I. MizzenL.A. Immunotherapy of a human papillomavirus (HPV) type 16 E7-expressing tumour by administration of fusion protein comprising Mycobacterium bovis bacille Calmette–Guérin (BCG) hsp65 and HPV16 E7.Clin. Exp. Immunol.2008121221622510.1046/j.1365‑2249.2000.01293.x10931134
     [Google Scholar]
  175. YangJ. LiS. GuoF. ZhangW. WangY. PanY. Induction of apoptosis by chitosan/HPV16 E7 siRNA complexes in cervical cancer cells.Mol. Med. Rep.201373998100210.3892/mmr.2012.124623258711
     [Google Scholar]
  176. ŞenelB. ÖztürkA.A. New approaches to tumor therapy with siRNA-decorated and chitosan-modified PLGA nanoparticles.Drug Dev. Ind. Pharm.201945111835184810.1080/03639045.2019.166506131491363
     [Google Scholar]
  177. BayerI.S. Hyaluronic acid and controlled release: A review.Molecules20202511264910.3390/molecules2511264932517278
     [Google Scholar]
  178. ZhangW. XuW. LanY. HeX. LiuK. LiangY. Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer.Int. J. Nanomedicine2019145287530110.2147/IJN.S20311331406460
     [Google Scholar]
  179. TomicicM.T. SteigerwaldC. RasenbergerB. BrozovicA. ChristmannM. Functional mismatch repair and inactive p53 drive sensitization of colorectal cancer cells to irinotecan via the IAP antagonist BV6.Arch. Toxicol.20199382265227710.1007/s00204‑019‑02513‑731289894
     [Google Scholar]
  180. HeichlerC. ScheibeK. SchmiedA. GeppertC.I. SchmidB. WirtzS. ThomaO.M. KramerV. WaldnerM.J. BüttnerC. FarinH.F. PešićM. KnielingF. MerkelS. GrüneboomA. GunzerM. GrützmannR. Rose-JohnS. KoralovS.B. KolliasG. ViethM. HartmannA. GretenF.R. NeurathM.F. NeufertC. STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis.Gut20206971269128210.1136/gutjnl‑2019‑31920031685519
     [Google Scholar]
  181. MoreiraC. OliveiraH. PiresL.R. SimõesS. BarbosaM.A. PêgoA.P. Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone.Acta Biomater.2009582995300610.1016/j.actbio.2009.04.02119427930
     [Google Scholar]
  182. KotzéA.R. LueβenH.L. de LeeuwB.J. de BoerB.G. VerhoefJ.C. JungingerH.E. N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: In vitro evaluation in intestinal epithelial cells (Caco-2).Pharm. Res.19971491197120210.1023/A:10121069077089327448
     [Google Scholar]
  183. SadioA. GustafssonJ.K. PereiraB. GomesC.P. HanssonG.C. DavidL. PêgoA.P. AlmeidaR. Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier.PLoS One201496e9944910.1371/journal.pone.009944924925340
     [Google Scholar]
  184. MasjediA. HassanniaH. AtyabiF. RastegariA. Hojjat-FarsangiM. NamdarA. SoleimanpourH. AziziG. NikkhooA. GhalamfarsaG. MirshafieyA. Jadidi- NiaraghF. Downregulation of A2AR by siRNA loaded PEG-chitosan-lactate nanoparticles restores the T cell mediated anti-tumor responses through blockage of PKA/CREB signaling pathway.Int. J. Biol. Macromol.201913343644510.1016/j.ijbiomac.2019.03.22330936011
     [Google Scholar]
  185. LayekB. HaldarM.K. SharmaG. LippL. MallikS. SinghJ. Hexanoic acid and polyethylene glycol double grafted amphiphilic chitosan for enhanced gene delivery: influence of hydrophobic and hydrophilic substitution degree.Mol. Pharm.201411398299410.1021/mp400633r24499512
     [Google Scholar]
  186. AgemyL. Friedmann-MorvinskiD. KotamrajuV.R. RothL. SugaharaK.N. GirardO.M. MattreyR.F. VermaI.M. RuoslahtiE. Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma.Proc. Natl. Acad. Sci. USA201110842174501745510.1073/pnas.111451810821969599
     [Google Scholar]
  187. El-SayedN.S. SharmaM. AliabadiH.M. El-MeligyM.G. El-ZaityA.K. NageibZ.A. TiwariR.K. Synthesis, characterization, and in vitro cytotoxicity of fatty acyl-CGKRK-chitosan oligosaccharides conjugates for siRNA delivery.Int. J. Biol. Macromol.201811269470210.1016/j.ijbiomac.2018.01.21329408713
     [Google Scholar]
  188. SievalA.B. ThanouM. Kotze´A.F. VerhoefJ.C. BrusseeJ. JungingerH.E. Preparation and NMR characterization of highly substitutedN-trimethyl chitosan chloride.Carbohydr. Polym.1998362-315716510.1016/S0144‑8617(98)00009‑5
     [Google Scholar]
  189. KamalzareS. NoormohammadiZ. RahimiP. AtyabiF. IraniS. TekieF.S.M. MottaghitalabF. Carboxymethyl dextran-trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV-1 Nef.J. Cell. Physiol.201923411205542056510.1002/jcp.2865531144311
     [Google Scholar]
  190. GargM. ShanmugamM.K. BhardwajV. GoelA. GuptaR. SharmaA. BaligarP. KumarA.P. GohB.C. WangL. SethiG. The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy.Med. Res. Rev.20214131291133610.1002/med.2176133289118
     [Google Scholar]
  191. NikkhooA. RostamiN. FarhadiS. EsmailyM. Moghadaszadeh ArdebiliS. AtyabiF. BaghaeiM. HaghnavazN. YousefiM. AliparastiM.R. GhalamfarsaG. MohammadiH. SojoodiM. Jadidi-NiaraghF. Codelivery of STAT3 siRNA and BV6 by carboxymethyl dextran trimethyl chitosan nanoparticles suppresses cancer cell progression.Int. J. Pharm.202058111923610.1016/j.ijpharm.2020.11923632240809
     [Google Scholar]
  192. YanT. ZhuS. HuiW. HeJ. LiuZ. ChengJ. Chitosan based pH-responsive polymeric prodrug vector for enhanced tumor targeted co-delivery of doxorubicin and siRNA.Carbohydr. Polym.202025011678110.1016/j.carbpol.2020.11678133049806
     [Google Scholar]
  193. ZhangS. GanY. ShaoL. LiuT. WeiD. YuY. GuoH. ZhuH. Virus mimetic shell-sheddable chitosan micelles for siVEGF delivery and FRET-traceable acid-triggered release.ACS Appl. Mater. Interfaces20201248535985361410.1021/acsami.0c1302333201664
     [Google Scholar]
  194. Clinicaltrials.2024Available from: https://clinicaltrials.gov [cited 2024 2024/3/11]
  195. SchultheisB. StrumbergD. SantelA. VankC. GebhardtF. KeilO. LangeC. GieseK. KaufmannJ. KhanM. DrevsJ. First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors.J. Clin. Oncol.201432364141414810.1200/JCO.2013.55.037625403217
     [Google Scholar]
  196. RundD. DaganM. Dalyot-HermanN. Kimchi-SarfatyC. SchoenleinP.V. GottesmanM.M. OppenheimA. Efficient transduction of human hematopoietic cells with the human multidrug resistance gene 1 via SV40 pseudovirions.Hum. Gene Ther.19989564965710.1089/hum.1998.9.5‑6499551613
     [Google Scholar]
  197. Kimchi-SarfatyC. Ben-Nun-ShaulO. RundD. OppenheimA. GottesmanM.M. In vitro-packaged SV40 pseudovirions as highly efficient vectors for gene transfer.Hum. Gene Ther.200213229931010.1089/1043034025276981511812285
     [Google Scholar]
  198. DannullJ. HaleyN.R. ArcherG. NairS. BoczkowskiD. HarperM. De RosaN. PickettN. MoscaP.J. BurchetteJ. SelimM.A. MitchellD.A. SampsonJ. TylerD.S. PruittS.K. Melanoma immunotherapy using mature DCs expressing the constitutive proteasome.J. Clin. Invest.201312373135314510.1172/JCI6754423934126
     [Google Scholar]
  199. KumthekarP. RademakerA. KoC. DixitK. SchwartzM.A. SonabendA.M. SharpL. LukasR.V. StuppR. HorbinskiC. McCortneyK. SteghA.H. A phase 0 first-in-human study using NU-0129: A gold base spherical nucleic acid (SNA) nanoconjugate targeting BCL2L12 in recurrent glioblastoma patients.J. Clin. Oncol.20193715_suppl3012301210.1200/JCO.2019.37.15_suppl.3012
     [Google Scholar]
  200. VargheseA.M. AngC. DimaioC.J. JavleM.M. GutierrezM. YaromN. StemmerS.M. GolanT. GevaR. SemenistyV. KhamaysiI. LigrestiR. RotkopfS. Gabai-MalkaR. GalunE. ShemiA. SchattnerM. O’ReillyE.M. A phase II study of siG12D-LODER in combination with chemotherapy in patients with locally advanced pancreatic cancer (PROTACT).J. Clin. Oncol.20203815_supplTPS4672TPS467210.1200/JCO.2020.38.15_suppl.TPS4672
     [Google Scholar]
  201. SargaziS. ArshadR. GhamariR. RahdarA. BakhshiA. KarkanS.F. AjalliN. BilalM. Díez-PascualA.M. siRNA-based nanotherapeutics as emerging modalities for immune-mediated diseases: A preliminary review.Cell Biol. Int.20224691320134410.1002/cbin.1184135830711
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673286052240426044945
Loading
Smart Physicochemical-triggered Chitosan-based Nanogels for siRNA Delivery and Gene Therapy: A Focus on Emerging Strategies and Paradigms for Cancer Therapy
Curr. Med. Chem. 32, 4913 (2025); https://doi.org/10.2174/0109298673286052240426044945
/content/journals/cmc/10.2174/0109298673286052240426044945
/content/journals/cmc/10.2174/0109298673286052240426044945
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): cancer therapy; chitosan; gene therapy; nanogel; siRNA; smart drug delivery

Most Cited Most Cited RSS feed

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