Skip to main content

Part of the book series: RNA Technologies ((RNATECHN))

  • 2047 Accesses

Abstract

The ability to detect pathways that malignant tissue depends on, combined with the specific gene-knockdown ability of siRNA/miRNA, may revolutionize cancer treatment. The capability of providing personalized care to cancer patients allows therapy to be specifically tailored for each case. Several studies of malignant and nonmalignant tissues have been performed in the context of global protein interaction networks in order to find the optimal targets, providing a list of potential gene and protein targets for each cancer type and for each patient. Nevertheless, due to poor stability of RNAi molecules in physiological conditions and its inability to cross cellular membranes, the in vivo delivery of siRNA and miRNA holds a great challenge and remains a crucial issue for its therapeutic success. Supramolecular carriers are often used in order to improve the physicochemical and biopharmaceutical properties of RNAi. Nanoscale drug delivery systems will enable the accumulation of the drugs in the tumors due to the enhanced permeability and retention (EPR) effect, and release the siRNA/miRNA only inside the target cell. In addition, a targeting moiety can increase the selectivity and specific uptake in the target tissue. Several vehicles (dendrimers, nanoparticles, polyplex, lipoplex, polymeric nanoconjugates) are being developed for siRNA/miRNA delivery. These vehicles provide an important tool for exploiting the full potential of nucleic acids as therapeutic agents. In this chapter, we will review the different approaches to deliver oligonucleotides in vivo.

Anna Scomparin and Galia Tiram contributed equally

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abrams MT, Koser ML, Seitzer J et al (2010) Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle: effect of dexamethasone co-treatment. Mol Ther 18:171–180

    Article  CAS  PubMed  Google Scholar 

  • Aleku M, Schulz P, Keil O et al (2008) Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res 68:9788–9798

    Article  CAS  PubMed  Google Scholar 

  • Amarzguioui M, Rossi JJ, Kim D (2005) Approaches for chemically synthesized siRNA and vector-mediated RNAi. FEBS Lett 579:5974–5981

    Article  CAS  PubMed  Google Scholar 

  • Arima H, Yoshimatsu A, Ikeda H et al (2012) Folate-PEG-appended dendrimer conjugate with alpha-cyclodextrin as a novel cancer cell-selective siRNA delivery carrier. Mol Pharm 9:2591–2604

    Article  CAS  PubMed  Google Scholar 

  • Asahina H, Yamazaki K, Kinoshita I et al (2006) A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. Br J Cancer 95:998–1004

    Article  CAS  PubMed  Google Scholar 

  • Behr JP, Demeneix B, Loeffler JP et al (1989) Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proc Natl Acad Sci USA 86:6982–6986

    Article  CAS  PubMed  Google Scholar 

  • Bologna JC, Dorn G, Natt F et al (2003) Linear polyethylenimine as a tool for comparative studies of antisense and short double-stranded RNA oligonucleotides. Nucleosides Nucleotides Nucleic Acids 22:1729–1731

    Article  CAS  PubMed  Google Scholar 

  • Boussif O, Lezoualc’h F, Zanta MA et al (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci USA 92:7297–7301

    Article  CAS  PubMed  Google Scholar 

  • Buhleier E, Wehner W, Vogtle F (1978) “Cascade” and “Nonskid-Chain-like” syntheses of molecular cavity topologies. Synthesis 2:155–158

    Article  Google Scholar 

  • Cervantes A, Alsina M, Tabernero J et al (2011) Phase I dose-escalation study of ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement. In: ASCO annual meeting, Journal of Clinical Oncology, Chicago, IL

    Google Scholar 

  • Chen H, Ma X, Li Z et al (2012) Functionalization of single-walled carbon nanotubes enables efficient intracellular delivery of siRNA targeting MDM2 to inhibit breast cancer cells growth. Biomed Pharmacother 66:334–338

    Article  CAS  PubMed  Google Scholar 

  • Choi JS, Lee EJ, Jang HS et al (2001) New cationic liposomes for gene transfer into mammalian cells with high efficiency and low toxicity. Bioconjug Chem 12:108–113

    Article  CAS  PubMed  Google Scholar 

  • Christie RJ, Matsumoto Y, Miyata K et al (2012) Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection. ACS Nano 6:5174–5189

    Article  CAS  PubMed  Google Scholar 

  • Dabkowska AP, Barlow DJ, Campbell RA et al (2012) Effect of helper lipids on the interaction of DNA with cationic lipid monolayers studied by specular neutron reflection. Biomacromolecules 13:2391–2401

    Article  CAS  PubMed  Google Scholar 

  • Daka A, Peer D (2012) RNAi-based nanomedicines for targeted personalized therapy. Adv Drug Deliv Rev 64:1508–1521

    Article  CAS  PubMed  Google Scholar 

  • Davidson BL, McCray PB Jr (2011) Current prospects for RNA interference-based therapies. Nat Rev Genet 12:329–340

    Article  CAS  PubMed  Google Scholar 

  • Davis ME, Zuckerman JE, Choi CH et al (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464:1067–1070

    Article  CAS  PubMed  Google Scholar 

  • de Fougerolles A, Vornlocher HP, Maraganore J et al (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 6:443–453

    Article  PubMed  CAS  Google Scholar 

  • de Martimprey H, Bertrand JR, Malvy C et al (2010) New core-shell nanoparticules for the intravenous delivery of siRNA to experimental thyroid papillary carcinoma. Pharm Res 27:498–509

    Article  PubMed  CAS  Google Scholar 

  • Derfus AM, Chen AA, Min DH et al (2007) Targeted quantum dot conjugates for siRNA delivery. Bioconjug Chem 18:1391–1396

    Article  CAS  PubMed  Google Scholar 

  • Dharmapuri S, Peruzzi D, Marra E et al (2011) Intratumor RNA interference of cell cycle genes slows down tumor progression. Gene Ther 18:727–733

    Article  CAS  PubMed  Google Scholar 

  • Dominska M, Dykxhoorn DM (2010) Breaking down the barriers: siRNA delivery and endosome escape. J Cell Sci 123:1183–1189

    Article  CAS  PubMed  Google Scholar 

  • Druker BJ, Guilhot F, O’Brien SG et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417

    Article  CAS  PubMed  Google Scholar 

  • Emi N, Kidoaki S, Yoshikawa K et al (1997) Gene transfer mediated by polyarginine requires a formation of big carrier-complex of DNA aggregate. Biochem Biophys Res Commun 231:421–424

    Article  CAS  PubMed  Google Scholar 

  • Felgner PL, Gadek TR, Holm M et al (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84:7413–7417

    Article  CAS  PubMed  Google Scholar 

  • Fire A, Xu S, Montgomery MK et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    Article  CAS  PubMed  Google Scholar 

  • Fischer W, Calderon M, Schulz A et al (2010) Dendritic polyglycerols with oligoamine shells show low toxicity and high siRNA transfection efficiency in vitro. Bioconjug Chem 21:1744–1752

    Article  CAS  PubMed  Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  CAS  PubMed  Google Scholar 

  • Fraley R, Subramani S, Berg P et al (1980) Introduction of liposome-encapsulated SV40 DNA into cells. J Biol Chem 255:10431–10435

    CAS  PubMed  Google Scholar 

  • Futreal PA, Coin L, Marshall M et al (2004) A census of human cancer genes. Nat Rev Cancer 4:177–183

    Article  CAS  PubMed  Google Scholar 

  • Gao X, Huang L (1991) A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem Biophys Res Commun 179:280–285

    Article  CAS  PubMed  Google Scholar 

  • Gao H, Hui KM (2001) Synthesis of a novel series of cationic lipids that can act as efficient gene delivery vehicles through systematic heterocyclic substitution of cholesterol derivatives. Gene Ther 8:855–863

    Article  CAS  PubMed  Google Scholar 

  • Gunasekaran K, Nguyen TH, Maynard HD et al (2011) Conjugation of siRNA with comb-type PEG enhances serum stability and gene silencing efficiency. Macromol Rapid Commun 32:654–659

    Article  CAS  PubMed  Google Scholar 

  • Gunther M, Lipka J, Malek A et al (2011) Polyethylenimines for RNAi-mediated gene targeting in vivo and siRNA delivery to the lung. Eur J Pharm Biopharm 77:438–449

    Article  PubMed  CAS  Google Scholar 

  • Guo J, Ogier JR, Desgranges S et al (2012) Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice. Biomaterials 33:7775–7784

    Article  CAS  PubMed  Google Scholar 

  • Hafez IM, Maurer N, Cullis PR (2001) On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther 8:1188–1196

    Article  CAS  PubMed  Google Scholar 

  • Hannon GJ, Rossi JJ (2004) Unlocking the potential of the human genome with RNA interference. Nature 431:371–378

    Article  CAS  PubMed  Google Scholar 

  • Harris JM, Chess RB (2003) Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2:214–221

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto T, Kawazu K, Nagasaki T et al (2012) Quantitative comparison between poly(L-arginine) and poly(L-lysine) at each step of polyplex-based gene transfection using a microinjection technique. Sci Technol Adv Mater 13:9–15

    Article  CAS  Google Scholar 

  • Heel RC, Brogden RN, Speight TM et al (1978) Tamoxifen: a review of its pharmacological properties and therapeutic use in the treatment of breast cancer. Drugs 16:1–24

    Article  CAS  PubMed  Google Scholar 

  • Herrero MA, Toma FM, Al-Jamal KT et al (2009) Synthesis and characterization of a carbon nanotube-dendron series for efficient siRNA delivery. J Am Chem Soc 131:9843–9848

    Article  CAS  PubMed  Google Scholar 

  • Howard KA (2009) Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev 61:710–720

    Article  CAS  PubMed  Google Scholar 

  • Huang HW, Chen FY, Lee MT (2004) Molecular mechanism of peptide-induced pores in membranes. Phys Rev Lett 92:198304

    Article  PubMed  CAS  Google Scholar 

  • Huang HY, Kuo WT, Chou MJ et al (2011) Co-delivery of anti-vascular endothelial growth factor siRNA and doxorubicin by multifunctional polymeric micelle for tumor growth suppression. J Biomed Mater Res A 97:330–338

    PubMed  Google Scholar 

  • Huh MS, Lee SY, Park S et al (2010) Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice. J Control Release 144:134–143

    Article  CAS  PubMed  Google Scholar 

  • Ilies MA, Johnson BH, Makori F et al (2005) Pyridinium cationic lipids in gene delivery: an in vitro and in vivo comparison of transfection efficiency versus a tetraalkylammonium congener. Arch Biochem Biophys 435:217–226

    Article  CAS  PubMed  Google Scholar 

  • Jain K, Kesharwani P, Gupta U et al (2010) Dendrimer toxicity: let’s meet the challenge. Int J Pharm 394:122–142

    Article  CAS  PubMed  Google Scholar 

  • Jeong JH, Mok H, Oh YK et al (2009) siRNA conjugate delivery systems. Bioconjug Chem 20:5–14

    Article  CAS  PubMed  Google Scholar 

  • Jevprasesphant R, Penny J, Jalal R et al (2003) The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int J Pharm 252:263–266

    Article  CAS  PubMed  Google Scholar 

  • Jin J, Bae KH, Yang H et al (2011) In vivo specific delivery of c-Met siRNA to glioblastoma using cationic solid lipid nanoparticles. Bioconjug Chem 22:2568–2572

    Article  CAS  PubMed  Google Scholar 

  • Jung S, Lee SH, Mok H et al (2010) Gene silencing efficiency of siRNA-PEG conjugates: effect of PEGylation site and PEG molecular weight. J Control Release 144:306–313

    Article  CAS  PubMed  Google Scholar 

  • Kam NW, Liu Z, Dai H (2005) Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J Am Chem Soc 127:12492–12493

    Article  CAS  PubMed  Google Scholar 

  • Katas H, Alpar HO (2006) Development and characterisation of chitosan nanoparticles for siRNA delivery. J Control Release 115:216–225

    Article  CAS  PubMed  Google Scholar 

  • Kearns MD, Donkor AM, Savva M (2008) Structure-transfection activity studies of novel cationic cholesterol-based amphiphiles. Mol Pharm 5:128–139

    Article  CAS  PubMed  Google Scholar 

  • Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385

    Article  CAS  PubMed  Google Scholar 

  • Kim TI, Seo HJ, Choi JS et al (2004) PAMAM-PEG-PAMAM: novel triblock copolymer as a biocompatible and efficient gene delivery carrier. Biomacromolecules 5:2487–2492

    Article  CAS  PubMed  Google Scholar 

  • Kim HR, Kim IK, Bae KH et al (2008) Cationic solid lipid nanoparticles reconstituted from low density lipoprotein components for delivery of siRNA. Mol Pharm 5:622–631

    Article  CAS  PubMed  Google Scholar 

  • Kircheis R, Wightman L, Wagner E (2001) Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev 53:341–358

    Article  CAS  PubMed  Google Scholar 

  • Kirpotin DB, Drummond DC, Shao Y et al (2006) Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res 66:6732–6740

    Article  CAS  PubMed  Google Scholar 

  • Kolhatkar RB, Kitchens KM, Swaan PW et al (2007) Surface acetylation of polyamidoamine (PAMAM) dendrimers decreases cytotoxicity while maintaining membrane permeability. Bioconjug Chem 18:2054–2060

    Article  CAS  PubMed  Google Scholar 

  • Krek A, Grun D, Poy MN et al (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500

    Article  CAS  PubMed  Google Scholar 

  • Landen CN Jr, Chavez-Reyes A, Bucana C et al (2005) Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res 65:6910–6918

    Article  CAS  PubMed  Google Scholar 

  • Lebleu B, Moulton HM, Abes R et al (2008) Cell penetrating peptide conjugates of steric block oligonucleotides. Adv Drug Deliv Rev 60:517–529

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Mok H, Lee Y et al (2011a) Self-assembled siRNA-PLGA conjugate micelles for gene silencing. J Control Release 152:152–158

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Mok H, Park TG (2011b) Di- and triblock siRNA-PEG copolymers: PEG density effect of polyelectrolyte complexes on cellular uptake and gene silencing efficiency. Macromol Biosci 11:410–418

    Article  CAS  PubMed  Google Scholar 

  • Lee JY, Lee SH, Oh MH et al (2012a) Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles. J Control Release 162:407–413

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, Huh MS, Lee SY et al (2012b) Tumor-homing poly-siRNA/glycol chitosan self-cross-linked nanoparticles for systemic siRNA delivery in cancer treatment. Angew Chem Int Ed Engl 51:7203–7207

    Article  CAS  PubMed  Google Scholar 

  • Li L, Shen Y (2009) Overcoming obstacles to develop effective and safe siRNA therapeutics. Expert Opin Biol Ther 9:609–619

    Article  CAS  PubMed  Google Scholar 

  • Liu P, Yu H, Sun Y et al (2012) A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery. Biomaterials 33:4403–4412

    Article  CAS  PubMed  Google Scholar 

  • Lobovkina T, Jacobson GB, Gonzalez-Gonzalez E et al (2011) In vivo sustained release of siRNA from solid lipid nanoparticles. ACS Nano 5:9977–9983

    Article  CAS  PubMed  Google Scholar 

  • Luten J, van Nostrum CF, De Smedt SC et al (2008) Biodegradable polymers as non-viral carriers for plasmid DNA delivery. J Control Release 126:97–110

    Article  CAS  PubMed  Google Scholar 

  • Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel) 3:1377–1397

    Article  CAS  Google Scholar 

  • Mao S, Sun W, Kissel T (2010) Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev 62:12–27

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto S, Christie RJ, Nishiyama N et al (2009) Environment-responsive block copolymer micelles with a disulfide cross-linked core for enhanced siRNA delivery. Biomacromolecules 10:119–127

    Article  CAS  PubMed  Google Scholar 

  • Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392

    CAS  PubMed  Google Scholar 

  • Miller K, Erez R, Segal E et al (2009) Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate. Angew Chem Int Ed Engl 48:2949–2954

    Article  CAS  PubMed  Google Scholar 

  • Mok H, Lee SH, Park JW et al (2010) Multimeric small interfering ribonucleic acid for highly efficient sequence-specific gene silencing. Nat Mater 9:272–278

    CAS  PubMed  Google Scholar 

  • Moschos SA, Jones SW, Perry MM et al (2007) Lung delivery studies using siRNA conjugated to TAT(48-60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjug Chem 18:1450–1459

    Article  CAS  PubMed  Google Scholar 

  • Muller RH, Mader K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art. Eur J Pharm Biopharm 50:161–177

    Article  CAS  PubMed  Google Scholar 

  • Namgung R, Kim WJ (2012) A highly entangled polymeric nanoconstruct assembled by siRNA and its reduction-trigged siRNA release for gene silencing. Small 8:3209–3219

    Article  CAS  PubMed  Google Scholar 

  • Nishina K, Unno T, Uno Y et al (2008) Efficient in vivo delivery of siRNA to the liver by conjugation of alpha-tocopherol. Mol Ther 16:734–740

    Article  CAS  PubMed  Google Scholar 

  • Ofek P, Fischer W, Calderon M et al (2010) In vivo delivery of small interfering RNA to tumors and their vasculature by novel dendritic nanocarriers. FASEB J 24:3122–3134

    Article  CAS  PubMed  Google Scholar 

  • Oishi M, Nagasaki Y, Itaka K et al (2005) Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells. J Am Chem Soc 127:1624–1625

    Article  CAS  PubMed  Google Scholar 

  • Olbrich C, Bakowsky U, Lehr CM et al (2001) Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA. J Control Release 77:345–355

    Article  CAS  PubMed  Google Scholar 

  • Ortiz Mellet C, Garcia Fernandez JM, Benito JM (2011) Cyclodextrin-based gene delivery systems. Chem Soc Rev 40:1586–1608

    Article  PubMed  CAS  Google Scholar 

  • Pangburn TO, Georgiou K, Bates FS et al (2012) Targeted polymersome delivery of siRNA induces cell death of breast cancer cells dependent upon Orai3 protein expression. Langmuir 28:12816–12830

    Article  CAS  PubMed  Google Scholar 

  • Parente RA, Nir S, Szoka FC Jr (1990) Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA. Biochemistry 29:8720–8728

    Article  CAS  PubMed  Google Scholar 

  • Pasqualini R, Koivunen E, Kain R et al (2000) Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res 60:722–727

    CAS  PubMed  Google Scholar 

  • Patil YB, Swaminathan SK, Sadhukha T et al (2010) The use of nanoparticle-mediated targeted gene silencing and drug delivery to overcome tumor drug resistance. Biomaterials 31:358–365

    Article  CAS  PubMed  Google Scholar 

  • Pierschbacher MD, Ruoslahti E (1984) Variants of the cell recognition site of fibronectin that retain attachment-promoting activity. Proc Natl Acad Sci USA 81:5985–5988

    Article  CAS  PubMed  Google Scholar 

  • Podesta JE, Al-Jamal KT, Herrero MA et al (2009) Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model. Small 5:1176–1185

    Article  CAS  PubMed  Google Scholar 

  • Raouane M, Desmaele D, Gilbert-Sirieix M et al (2011) Synthesis, characterization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma. J Med Chem 54:4067–4076

    Article  CAS  PubMed  Google Scholar 

  • Remy JS, Sirlin C, Vierling P et al (1994) Gene transfer with a series of lipophilic DNA-binding molecules. Bioconjug Chem 5:647–654

    Article  CAS  PubMed  Google Scholar 

  • Ribas A, Kalinoski L, Heidel JD et al (2010) Systemic delivery of siRNA via targeted nanoparticles in patients with cancer: results from a first-in-class phase I clinical trial. In: ASCO annual meeting, Chicago, IL

    Google Scholar 

  • Rozema DB, Lewis DL, Wakefield DH et al (2007) Dynamic polyconjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc Natl Acad Sci USA 104:12982–12987

    Article  CAS  PubMed  Google Scholar 

  • Saranya N, Moorthi A, Saravanan S et al (2011) Chitosan and its derivatives for gene delivery. Int J Biol Macromol 48:234–238

    Article  CAS  PubMed  Google Scholar 

  • Segal E, Pan H, Ofek P et al (2009) Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PLoS One 4:e5233

    Article  PubMed  CAS  Google Scholar 

  • Semple SC, Harasym TO, Clow KA et al (2005) Immunogenicity and rapid blood clearance of liposomes containing polyethylene glycol-lipid conjugates and nucleic acid. J Pharmacol Exp Ther 312:1020–1026

    Article  CAS  PubMed  Google Scholar 

  • Semple SC, Akinc A, Chen J et al (2010) Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28:172–176

    Article  CAS  PubMed  Google Scholar 

  • Seymour LW, Ferry DR, Anderson D et al (2002) Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J Clin Oncol 20:1668–1676

    Article  CAS  PubMed  Google Scholar 

  • Soutschek J, Akinc A, Bramlage B et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178

    Article  CAS  PubMed  Google Scholar 

  • Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458:719–724

    Article  CAS  PubMed  Google Scholar 

  • Strumberg D, Schultheis B, Traugott U et al (2012) Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors. Int J Clin Pharmacol Ther 50:76–78

    CAS  PubMed  Google Scholar 

  • Sun TM, Du JZ, Yao YD et al (2011) Simultaneous delivery of siRNA and paclitaxel via a “two-in-one” micelleplex promotes synergistic tumor suppression. ACS Nano 5:1483–1494

    Article  CAS  PubMed  Google Scholar 

  • Taratula O, Garbuzenko OB, Kirkpatrick P et al (2009) Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery. J Control Release 140:284–293

    Article  CAS  PubMed  Google Scholar 

  • Tekmira (2012) http://investor.tekmirapharm.com/releasedetail.cfm?ReleaseID=700453

  • Tros de Ilarduya C, Sun Y, Duzgunes N (2010) Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40:159–170

    Article  CAS  PubMed  Google Scholar 

  • Tsai LR, Chen MH, Chien CT et al (2011) A single-monomer derived linear-like PEI-co-PEG for siRNA delivery and silencing. Biomaterials 32:3647–3653

    Article  CAS  PubMed  Google Scholar 

  • Ulbrich K, Etrych T, Chytil P et al (2004) Antibody-targeted polymer-doxorubicin conjugates with pH-controlled activation. J Drug Target 12:477–489

    Article  CAS  PubMed  Google Scholar 

  • Urban-Klein B, Werth S, Abuharbeid S et al (2005) RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther 12:461–466

    Article  CAS  PubMed  Google Scholar 

  • Vogel CL, Cobleigh MA, Tripathy D et al (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Ren J, Qu X (2008) Targeted RNA interference of cyclin A2 mediated by functionalized single-walled carbon nanotubes induces proliferation arrest and apoptosis in chronic myelogenous leukemia K562 cells. ChemMedChem 3:940–945

    Article  CAS  PubMed  Google Scholar 

  • Wu GY, Wu CH (1988) Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro. Biochemistry 27:887–892

    Article  CAS  PubMed  Google Scholar 

  • Xia W, Wang P, Lin C et al (2012) Bioreducible polyethylenimine-delivered siRNA targeting human telomerase reverse transcriptase inhibits HepG2 cell growth in vitro and in vivo. J Control Release 157:427–436

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Szoka FC Jr (1996) Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35:5616–5623

    Article  CAS  PubMed  Google Scholar 

  • Xue HY, Wong HL (2011) Tailoring nanostructured solid-lipid carriers for time-controlled intracellular siRNA kinetics to sustain RNAi-mediated chemosensitization. Biomaterials 32:2662–2672

    Article  CAS  PubMed  Google Scholar 

  • York AW, Huang F, McCormick CL (2010) Rational design of targeted cancer therapeutics through the multiconjugation of folate and cleavable siRNA to RAFT-synthesized (HPMA-s-APMA) copolymers. Biomacromolecules 11:505–514

    Article  CAS  PubMed  Google Scholar 

  • Yu YH, Kim E, Park DE et al (2012) Cationic solid lipid nanoparticles for co-delivery of paclitaxel and siRNA. Eur J Pharm Biopharm 80:268–273

    Article  CAS  PubMed  Google Scholar 

  • Zelphati O, Szoka FC Jr (1996) Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci USA 93:11493–11498

    Article  CAS  PubMed  Google Scholar 

  • Zhang JS, Liu F, Huang L (2005) Implications of pharmacokinetic behavior of lipoplex for its inflammatory toxicity. Adv Drug Deliv Rev 57:689–698

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Patel TR, Fu M et al (2012) Octa-functional PLGA nanoparticles for targeted and efficient siRNA delivery to tumors. Biomaterials 33:583–591

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ronit Satchi-Fainaro .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Scomparin, A., Tiram, G., Satchi-Fainaro, R. (2013). Nanoscale-Based Delivery of RNAi for Cancer Therapy. In: Erdmann, V., Barciszewski, J. (eds) DNA and RNA Nanobiotechnologies in Medicine: Diagnosis and Treatment of Diseases. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36853-0_14

Download citation

Publish with us

Policies and ethics