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Efficient nanocarriers of siRNA therapeutics for cancer treatment

  • Md Abdus Subhan
    Correspondence
    Reprint requests: Md Abdus Subhan, Department of Chemistry, Shah Jalal University of Science and Technology, Sylhet 3114, Bangladesh.
    Affiliations
    Department of Pharmaceutical Sciences, CPBN, Northeastern University, Boston, Massachusetts

    Department of Chemistry, Shah Jalal University of Science and Technology, Sylhet, Bangladesh
    Search for articles by this author
  • V.P. Torchilin
    Affiliations
    Department of Pharmaceutical Sciences, CPBN, Northeastern University, Boston, Massachusetts
    Search for articles by this author
      Nanocarriers as drug delivery systems are promising and becoming popular, especially for cancer treatment. In addition to improving the pharmacokinetics of poorly soluble hydrophobic drugs by solubilizing them in a hydrophobic core, nanocarriers allow cancer-specific combination drug deliveries by inherent passive targeting phenomena and adoption of active targeting strategies. Nanoparticle-drug formulations can enhance the safety, pharmacokinetic profiles, and bioavailability of locally or systemically administered drugs, leading to improved therapeutic efficacy. Gene silencing by RNA interference (RNAi) is rapidly developing as a personalized field of cancer treatment. Small interfering RNAs (siRNAs) can be used to switch off specific cancer genes, in effect, “silence the gene, silence the cancer.” siRNA can be used to silence specific genes that produce harmful or abnormal proteins. The activity of siRNA can be used to harness cellular machinery to destroy a corresponding sequence of mRNA that encodes a disease-causing protein. At present, the main barrier to implementing siRNA therapies in clinical practice is the lack of an effective delivery system that protects the siRNA from nuclease degradation, delivers to it to cancer cells, and releases it into the cytoplasm of targeted cancer cells, without creating adverse effects. This review provides an overview of various nanocarrier formulations in both research and clinical applications with a focus on combinations of siRNA and chemotherapeutic drug delivery systems for the treatment of multidrug resistant cancer. The use of various nanoparticles for siRNA-drug delivery, including liposomes, polymeric nanoparticles, dendrimers, inorganic nanoparticles, exosomes, and red blood cells for targeted drug delivery in cancer is discussed.

      Abbreviations:

      ACC (adrenocortical carcinoma), AKI (acute kidney injury), AD-PEG-Tf (adamantane-PEG-transferrin), ALDH2 (aldehyde dehydrogenase 2), Ang-2 (angiopoietin-2), BSA (bovine serum albumin), CDP (dyclodextrin polymer), DPCs (dynamic polyconjugates), DOPC (1, 2-dioleoylsn-glycero-3-phosphatidylcholine), DOPE (dioleoylphosphatidylethanolamine), DOTAP (dioleoyl-phosphatidylethanol-amine and 1,2-dioleoyl-3- trimethylammonium-propane), DGF (delayed graft function), EV (extracellular vehicle), EphA2 (Ephrin type-A receptor 2), EPR (enhanced permeability and retention), FAP (familial adenomatous polyposis), FDA (Food and Drug Administration), GI-NET (gastrointestinal neuroendocrine tumors), GFP (green fluorescence protein), HBFC (heterobifunctional cross-linker), HEMA (histidine-methacrylic acid), HCC (hepatocellular carcinoma), i.v. (intravenous), i.p. (intraperitoneal), KSP (kinesin spindle protein), LPS (lipopolysaccharide), LNP (lipid nanoparticle), MMP-2 (matrix metallo-proteinase-2), MAPK-1 (mitogen-activated protein kinase1), miRNA (microRNA), NCs (nanocarriers), NLRs (nucleotide-binding oligomerization domain (NOD)-like receptors), GalNAc (N-acetylgalactosamine), PEI (polyethylenimine), NSCLC (non–small-cell lung cancer), ONPs (oligonucleotide nanoparticles), PSMA (prostate-specific membrane antigen), PEG (polyethylene glycol), PKN3 (protein kinase N3), G4 PAMAM (4 polyamidoamine), PCL (polycaprolactone), PLA (poly(d,l-lactide)), PLGA (poly(d,l-lactide-co-glycolide)), PPEEA (poly(ethylene glycol)-block-poly(ε-caprolactone)-blockpoly(2-aminoethyl ethylene phosphate)), PBMC (peripheral blood mononuclear cells), RNAi (RNA interference), RISC (RNA-induced silencing complex), RVG (rabies virus glycoprotein), siRNAs (small interfering RNAs), RES (reticuloendothelial system), ssRNA (single-stranded RNA), SNALP (stable nucleic acid lipid particle), TCM (triblock co-polymer micelle), hATTR-PN (transthyretin-mediated Amyloidosis with polyneuropathy), PLK-1 (polo-like kinase protein), VEGF (vascular endothelial growth factor)
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