Therapeutic Applications of Spherical Nucleic Acids

Part of the Cancer Treatment and Research book series (CTAR, volume 166)


Spherical nucleic acids (SNAs) represent an emerging class of nanoparticle-based therapeutics. SNAs consist of densely functionalized and highly oriented oligonucleotides on the surface of a nanoparticle which can either be inorganic (such as gold or platinum) or hollow (such as liposomal or silica-based). The spherical architecture of the oligonucleotide shell confers unique advantages over traditional nucleic acid delivery methods, including entry into nearly all cells independent of transfection agents and resistance to nuclease degradation. Furthermore, SNAs can penetrate biological barriers, including the blood–brain and blood–tumor barriers as well as the epidermis, and have demonstrated efficacy in several murine disease models in the absence of significant adverse side effects. In this chapter, we will focus on the applications of SNAs in cancer therapy as well as discuss multimodal SNAs for drug delivery and imaging.


Spherical nucleic acids SNAs siRNA Nanoparticles Cancer Therapeutics 


  1. 1.
    Burnett JC, Rossi JJ, Tiemann K (2011) Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J 6(9):1130–1146PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Stegh AH (2013) Toward personalized cancer nanomedicine—past, present, and future. Integr Biol 5(1):48–65CrossRefGoogle Scholar
  3. 3.
    Burnett JC, Rossi JJ (2012) RNA-based therapeutics: current progress and future prospects. Chem Biol 19(1):60–71PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Davidson BL, McCray PB (2011) Current prospects for RNA interference-based therapies. Nat Rev Genet 12(5):329–340PubMedCrossRefGoogle Scholar
  5. 5.
    Kanasty R, Dorkin JR, Vegas A, Anderson D (2013) Delivery materials for siRNA therapeutics. Nat Mater 12(11):967–977PubMedCrossRefGoogle Scholar
  6. 6.
    Kim DH, Rossi JJ (2007) Strategies for silencing human disease using RNA interference. Nat Rev Genet 8(3):173–184PubMedCrossRefGoogle Scholar
  7. 7.
    Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642–655PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Bennett CF, Swayze EE (2010) RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 50:259–293PubMedCrossRefGoogle Scholar
  9. 9.
    Magen I, Hornstein E (2014) Oligonucleotide-based therapy for neurodegenerative diseases. Brain Res 1584:116–128PubMedCrossRefGoogle Scholar
  10. 10.
    Cerritelli SM, Crouch RJ (2009) Ribonuclease H: the enzymes in eukaryotes. FEBS J 276(6):1494–1505PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811PubMedCrossRefGoogle Scholar
  12. 12.
    Castanotto D, Rossi JJ (2009) The promises and pitfalls of RNA-interference-based therapeutics. Nature 457(7228):426–433PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498PubMedCrossRefGoogle Scholar
  14. 14.
    Hannon GJ, Rossi JJ (2004) Unlocking the potential of the human genome with RNA interference. Nature 431(7006):371–378PubMedCrossRefGoogle Scholar
  15. 15.
    Novina CD, Sharp PA (2004) The RNAi revolution. Nature 430(6996):161–164PubMedCrossRefGoogle Scholar
  16. 16.
    Hannon GJ (2002) RNA interference. Nature 418(6894):244–251PubMedCrossRefGoogle Scholar
  17. 17.
    McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3(10):737–747PubMedCrossRefGoogle Scholar
  18. 18.
    Zamore PD, Tuschl T, Sharp PA, Bartel DP (2000) RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101(1):25–33PubMedCrossRefGoogle Scholar
  19. 19.
    Bartlett DW, Davis ME (2007) Effect of siRNA nuclease stability on the in vitro and in vivo kinetics of siRNA-mediated gene silencing. Biotechnol Bioeng 97(4):909–921PubMedCrossRefGoogle Scholar
  20. 20.
    Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379PubMedCrossRefGoogle Scholar
  21. 21.
    Kanasty RL, Whitehead KA, Vegas AJ, Anderson DG (2012) Action and reaction: the biological response to siRNA and Its delivery vehicles. Mol Ther 20(3):513–524PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Schroeder A, Levins CG, Cortez C, Langer R, Anderson DG (2010) Lipid-based nanotherapeutics for siRNA delivery. J Intern Med 267(1):9–21PubMedCrossRefGoogle Scholar
  23. 23.
    Whitehead KA, Langer R, Anderson DG (2010) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 9(5):412CrossRefGoogle Scholar
  24. 24.
    Fichter KM, Ingle NP, McLendon PM, Reineke TM (2013) Polymeric nucleic acid vehicles exploit active interorganelle trafficking mechanisms. ACS Nano 7(1):347–364PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Nelson CE, Kintzing JR, Hanna A, Shannon JM, Gupta MK, Duvall CL (2013) Balancing cationic and hydrophobic content of PEGylated siRNA polyplexes enhances endosome escape, stability, blood circulation time, and bioactivity in vivo. ACS Nano 7(10):8870–8880PubMedCrossRefGoogle Scholar
  26. 26.
    Patil ML, Zhang M, Taratula O, Garbuzenko OB, He H, Minko T (2009) Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: effect of the degree of quaternization and cancer targeting. Biomacromolecules 10(2):258–266PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Alabi CA, Love KT, Sahay G, Yin H, Luly KM, Langer R, Anderson DG (2013) Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery. Proc Natl Acad Sci USA 110(32):12881–12886PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Rungta RL, Choi HB, Lin PJC, Ko RWY, Ashby D, Nair J, Manoharan M, Cullis PR, MacVicar BA (2013) Lipid nanoparticle delivery of siRNA to silence neuronal gene expression in the brain. Mol Ther Nucleic Acids 2:e136PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Nayerossadat N, Maedeh T, Ali PA (2012) Viral and nonviral delivery systems for gene delivery. Adv Biomed Res 1(2):14Google Scholar
  30. 30.
    Bharali DJ, Klejbor I, Stachowiak EK, Dutta P, Roy I, Kaur N, Bergey EJ, Prasad PN, Stachowiak MK (2005) Organically modified silica nanoparticles: a nonviral vector for in vivo gene delivery and expression in the brain. Proc Natl Acad Sci USA 102(32):11539–11544PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA (2010) Gold nanoparticles for biology and medicine. Angew Chem Int Ed 49(19):3280–3294CrossRefGoogle Scholar
  32. 32.
    Kneuer C, Sameti M, Bakowsky U, Schiestel T, Schirra H, Schmidt H, Lehr C-M (2000) A nonviral DNA delivery system based on surface modified silica-nanoparticles can efficiently transfect cells in vitro. Bioconjug Chem 11(6):926–932PubMedCrossRefGoogle Scholar
  33. 33.
    Cutler JI, Auyeung E, Mirkin CA (2012) Spherical nucleic acids. J Am Chem Soc 134(3):1376–1391PubMedCrossRefGoogle Scholar
  34. 34.
    Mirkin CA, Letsinger RL, Mucic RC, Storhoff JJ (1996) A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382(15):607–609PubMedCrossRefGoogle Scholar
  35. 35.
    Giljohann DA, Seferos DS, Patel PC, Millstone JE, Rosi NL, Mirkin CA (2007) Oligonucleotide loading determines cellular uptake of DNA-modified gold nanoparticles. Nano Lett 7(12):3818–3821PubMedCrossRefGoogle Scholar
  36. 36.
    Choi CHJ, Hao L, Narayan SP, Auyeung E, Mirkin CA (2013) Mechanism for the endocytosis of spherical nucleic acid nanoparticle conjugates. Proc Natl Acad Sci USA 110(19):7625–7630PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Patel PC, Giljohann DA, Daniel WL, Zheng D, Prigodich AE, Mirkin CA (2010) Scavenger receptors mediate cellular uptake of polyvalent oligonucleotide-functionalized gold nanoparticles. Bioconjug Chem 21(12):2250–2256PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Massich MD, Giljohann DA, Seferos DS, Ludlow LE, Horvath CM, Mirkin CA (2009) Regulating immune response using polyvalent nucleic acid—gold nanoparticle conjugates. Mol Biopharm 6(6):1934–1940CrossRefGoogle Scholar
  39. 39.
    Zheng D, Giljohann DA, Chen DL, Massich MD, Wang XQ, Iordanov H, Mirkin CA, Paller AS (2012) Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. Proc Natl Acad Sci USA 109(30):11975–11980PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Barnaby SN, Lee A, Mirkin CA (2014) Probing the inherent stability of siRNA immobilized on nanoparticle constructs. Proc Natl Acad Sci USA 111(27):9739–9744PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Giljohann DA, Seferos DS, Prigodich AE, Patel PC, Mirkin CA (2009) Gene regulation with polyvalent siRNA—nanoparticle conjugates. J Am Chem Soc 131(6):2072–2073PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean AKR, Han MS, Mirkin CA (2006) Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312(5776):1027–1030PubMedCrossRefGoogle Scholar
  43. 43.
    Seferos DS, Prigodich AE, Giljohann DA, Patel PC, Mirkin CA (2009) Polyvalent DNA nanoparticle conjugates stabilize nucleic acids. Nano Lett 9(1):308–311PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Hao L, Patel PC, Alhasan AH, Giljohann DA, Mirkin CA (2011) Nucleic acid-gold nanoparticle conjugates as mimics of microRNA. Small 7(22):3158–3162PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP, Kouri FM, Merkel TJ, Luthi AJ, Patel PC, Cutler JI, Daniel WL, Scott AW, Rotz MW, Meade TJ, Giljohann DA, Mirkin CA, Stegh AH (2013) Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Transl Med 5(209):209ra152Google Scholar
  46. 46.
    Lee J-S, Lytton-Jean AKR, Hurst SJ, Mirkin CA (2007) Silver nanoparticle—oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties. Nano Lett 7(7):2112–2115PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Cutler JI, Zheng D, Xu X, Giljohann DA, Mirkin CA (2010) Polyvalent oligonucleotide iron oxide nanoparticle “click” conjugates. Nano Lett 10(4):1477–1480PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Zhang C, Macfarlane RJ, Young KL, Choi CHJ, Hao L, Auyeung E, Liu G, Zhou X, Mirkin CA (2013) A general approach to DNA-programmable atom equivalents. Nat Mater 12(8):741–746PubMedCrossRefGoogle Scholar
  49. 49.
    Mitchell GP, Mirkin CA, Letsinger RL (1999) Programmed assembly of DNA functionalized quantum dots. J Am Chem Soc 121(35):8122–8123CrossRefGoogle Scholar
  50. 50.
    Young KL, Scott AW, Hao L, Mirkin SE, Liu G, Mirkin CA (2012) Hollow spherical nucleic acids for intracellular gene regulation based upon biocompatible silica shells. Nano Lett 12(7):3867–3871PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Banga RJ, Chernyak N, Narayan SP, Nguyen ST, Mirkin CA (2014) Liposomal spherical nucleic acids. J Am Chem Soc 136(28):9866–9869PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Calabrese CM, Merkel TJ, Briley WE, Randeria PS, Narayan SP, Rouge JL, Walker DA, Scott AW, Mirkin CA (2015) Biocompatible infinite-coordination-polymer-nanoparticle—nucleic-acid conjugates for antisense gene regulation Angew Chem Int Ed 54(2):476−480Google Scholar
  53. 53.
    Cutler JI, Zhang K, Zheng D, Auyeung E, Prigodich AE, Mirkin CA (2011) Polyvalent nucleic acid nanostructures. J Am Chem Soc 133(24):9254–9257PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Morris W, Briley WE, Auyeung E, Cabezas MD, Mirkin CA (2014) Nucleic acid-metal organic framework (MOF) nanoparticle conjugates. J Am Chem Soc 136(20):7261–7264PubMedCrossRefGoogle Scholar
  55. 55.
    Alemdaroglu FE, Alemdaroglu NC, Langguth P, Herrmann A (2008) DNA block copolymer micelles—a combinatorial tool for cancer nanotechnology. Adv Mater 20(5):899–902CrossRefGoogle Scholar
  56. 56.
    Li Z, Zhang Y, Fullhart P, Mirkin CA (2004) Reversible and chemically programmable micelle assembly with DNA block-copolymer amphiphiles. Nano Lett 4(6):1055–1058CrossRefGoogle Scholar
  57. 57.
    Rouge JL, Hao L, Wu XA, Briley WE, Mirkin CA (2014) Spherical nucleic acids as a divergent platform for synthesizing RNA-nanoparticle conjugates through enzymatic ligation. ACS Nano 8(9):8837–8843PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5(4):505–515PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Kommareddy S, Amiji M (2007) Biodistribution and pharmacokinetic analysis of long-circulating thiolated gelatin nanoparticles following systemic administration in breast cancer-bearing mice. J Pharm Sci 96(2):397–407PubMedCrossRefGoogle Scholar
  60. 60.
    Zhang K, Hao L, Hurst SJ, Mirkin CA (2012) Antibody-linked spherical nucleic acids for cellular targeting. J Am Chem Soc 134(40):16488–16491PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Nanba D, Toki F, Barrandon Y, Higashiyama S (2013) Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation. J Dermatol Sci 72(2):81–86PubMedCrossRefGoogle Scholar
  62. 62.
    Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, Sabel M, Steinbach JP, Heese O, Reifenberger G, Weller M, Schackert G, Network ftGG (2007) Long-term survival with glioblastoma multiforme. Brain 130(10):2596–2606PubMedCrossRefGoogle Scholar
  63. 63.
    Pardridge WM (2012) Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab 32(11):1959–1972PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Goti D, Hrzenjak A, Levak-Frank S, Frank S, Van Der Westhuyzen DR, Malle E, Sattler W (2001) Scavenger receptor class B, type I is expressed in porcine brain capillary endothelial cells and contributes to selective uptake of HDL-associated vitamin E. J Neurochem 76(2):498–508PubMedCrossRefGoogle Scholar
  65. 65.
    Mackic JB, Stins M, McComb JG, Calero M, Ghiso J, Kim KS, Yan SD, Stern D, Schmidt AM, Frangione B, Zlokovic BV (1998) Human blood-brain barrier receptors for Alzheimer’s amyloid-beta 1–40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer. J Clin Invest 102(4):734–743PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Stegh AH, Brennan C, Mahoney JA, Forloney KL, Jenq HT, Luciano JP, Protopopov A, Chin L, DePinho RA (2010) Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor. Genes Dev 24(19):2194–2204PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Stegh AH, Chin L, Louis DN, DePinho RA (2008) What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? A role for Bcl2L12 as a multifunctional cell death regulator. Cell Cycle 7(18):2833–2839PubMedCrossRefGoogle Scholar
  68. 68.
    Stegh AH, DePinho RA (2011) Beyond effector caspase inhibition Bcl2L12 neutralizes p53 signaling in glioblastoma. Cell Cycle 10(1):33–38PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Stegh AH, Kesari S, Mahoney JE, Jenq HT, Forloney KL, Protopopov A, Louis DN, Chin L, DePinho RA (2008) Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma. Proc Natl Acad Sci USA 105(31):10703–10708PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, Schulze H, Park K, Hannon GJ, Yuan J, Louis DN, DePinho RA, Chin L (2007) Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. Genes Dev 21(1):98–111PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Boveri M, Berezowski V, Price A, Slupek S, Lenfant A-M, Benaud C, Hartung T, Cecchelli R, Prieto P, Dehouck M-P (2005) Induction of blood-brain barrier properties in cultured brain capillary endothelial cells: comparison between primary glial cells and C6 cell line. Glia 51(3):187–198PubMedCrossRefGoogle Scholar
  72. 72.
    Cecchelli R, Dehouck B, Descamps L, Fenart L, Buée-Scherrer V, Duhem C, Lundquist S, Rentfel M, Torpier G, Dehouck MP (1999) In vitro model for evaluating drug transport across the blood–brain barrier. Adv Drug Deliv Rev 36(2–3):165–178PubMedCrossRefGoogle Scholar
  73. 73.
    Culot M, Lundquist S, Vanuxeem D, Nion S, Landry C, Delplace Y, Dehouck M-P, Berezowski V, Fenart L, Cecchelli R (2008) An in vitro blood-brain barrier model for high throughput (HTS) toxicological screening. Toxicol In Vitro 22(3):799–811PubMedCrossRefGoogle Scholar
  74. 74.
    Petros RA, DeSimone JM (2010) Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov 9(8):615–627PubMedCrossRefGoogle Scholar
  75. 75.
    Huse JT, Holland EC (2009) Yin and yang: cancer-implicated miRNAs that have it both ways. Cell Cycle 8(22):3611–3612PubMedCrossRefGoogle Scholar
  76. 76.
    Iorio MV, Croce CM (2009) MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 27(34):5848–5856PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Iorio MV, Croce CM (2012) Causes and Consequences of MicroRNA dysregulation. Cancer J 18(3):215–222 210.1097/PPO.1090b1013e318250c318001Google Scholar
  78. 78.
    Kouri FM, Hurley LA, Day ES, Hua Y, Merkel TJ, Queisser MA, Peng C-Y, Ritner C, Hao L, Daniel WL, Zhang H, Sznajder JI, Chin L, Giljohann DA, Kessler JA, Peter ME, Mirkin CA, Stegh AH (2015) miR-182 integrates apoptosis, growth and differentiation programs in glioblastoma Genes and Development, in pressGoogle Scholar
  79. 79.
    Cancer Genome Atlas Research N (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216):1061–1068CrossRefGoogle Scholar
  80. 80.
    Geusens B, Sanders N, Prow T, Van Gele M, Lambert J (2009) Cutaneous short-interfering RNA therapy. Expert Opin Drug Deliv 6(12):1333–1349PubMedCrossRefGoogle Scholar
  81. 81.
    Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM, Hansen CD, Eliason MJ, Srivatsa GS, Kornbrust DJ, Smith FJD, McLean WHI, Milstone LM, Kaspar RL (2009) First-in-human mutation-targeted siRNA Phase Ib trial of an inherited skin disorder. Mol Ther 18(2):442–446PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Proksch E, Brandner JM, Jensen J-M (2008) The skin: an indispensable barrier. Exp Dematol 17(12):1063–1072CrossRefGoogle Scholar
  83. 83.
    Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310PubMedCrossRefGoogle Scholar
  84. 84.
    Zhu H, Acquaviva J, Ramachandran P, Boskovitz A, Woolfenden S, Pfannl R, Bronson RT, Chen JW, Weissleder R, Housman DE, Charest A (2009) Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc Natl Acad Sci USA 106(8):2712–2716PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Dickens S, Van den Berge S, Hendrickx B, Verdonck K, Luttun A, Vranckx JJ (2010) Nonviral transfection strategies for keratinocytes, fibroblasts, and endothelial progenitor cells for ex vivo gene transfer to skin wounds. Tissue Eng Part C Methods 16(6):1601–1608PubMedCrossRefGoogle Scholar
  86. 86.
    Jamieson ER, Lippard SJ (1999) Structure, recognition, and processing of cisplatin—DNA adducts. Chem Rev 99(9):2467–2498PubMedCrossRefGoogle Scholar
  87. 87.
    Rosenberg B, Vancamp L, Trosko JE, Mansour VH (1969) Platinum compounds: a new class of potent antitumour agents. Nature 222(5191):385–386PubMedCrossRefGoogle Scholar
  88. 88.
    Lorusso D, Petrelli F, Coinu A, Raspagliesi F, Barni S (2014) A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol 133(1):117–123PubMedCrossRefGoogle Scholar
  89. 89.
    Dhar S, Daniel WL, Giljohann DA, Mirkin CA, Lippard SJ (2009) Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads. J Am Chem Soc 131(41):14652–14653PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Wang D, Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4(4):307–320PubMedCrossRefGoogle Scholar
  91. 91.
    Zhang X-Q, Xu X, Lam R, Giljohann D, Ho D, Mirkin CA (2011) Strategy for increasing drug solubility and efficacy through covalent attachment to polyvalent DNA–nanoparticle conjugates. ACS Nano 5(9):6962–6970PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Dubois J (2006) Recent progress in the development of docetaxel and paclitaxel analogues. Expert Opin Ther Pat 16(11):1481–1496CrossRefGoogle Scholar
  93. 93.
    Marupudi NI, Han JE, Li KW, Renard VM, Tyler BM, Brem H (2007) Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin Drug Saf 6(5):609–621PubMedCrossRefGoogle Scholar
  94. 94.
    Panchagnula R (1998) Pharmaceutical aspects of paclitaxel. Int J Pharm 172(1–2):1–15CrossRefGoogle Scholar
  95. 95.
    Skwarczynski M, Hayashi Y, Kiso Y (2006) Paclitaxel prodrugs: toward smarter delivery of anticancer agents. J Med Chem 49(25):7253–7269PubMedCrossRefGoogle Scholar
  96. 96.
    Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119(3):493–501PubMedCrossRefGoogle Scholar
  97. 97.
    Baselga J, Swain SM (2009) Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 9(7):463–475PubMedCrossRefGoogle Scholar
  98. 98.
    Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354PubMedCrossRefGoogle Scholar
  99. 99.
    Hendriks BS, Opresko LK, Wiley HS, Lauffenburger D (2003) Quantitative analysis of HER2-mediated effects on HER2 and epidermal growth factor receptor endocytosis: distribution of homo- and heterodimers depends on relative HER2 levels. J Biol Chem 278(26):23343–23351PubMedCrossRefGoogle Scholar
  100. 100.
    Song Y, Xu X, MacRenaris KW, Zhang X-Q, Mirkin CA, Meade TJ (2009) Multimodal gadolinium-enriched DNA–gold nanoparticle conjugates for cellular imaging. Angew Chem Int Ed 121(48):9307–9311CrossRefGoogle Scholar
  101. 101.
    Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F (2002) Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J Magn Reson Imaging 16(4):394–406PubMedCrossRefGoogle Scholar
  102. 102.
    Bloembergen N (1956) Spin relaxation processes in a two-proton system. Phys Rev 104(6):1542–1547CrossRefGoogle Scholar
  103. 103.
    Bloembergen N (1957) Proton relaxation times in paramagnetic solutions. Chem Phys 27(2):572–573Google Scholar
  104. 104.
    Bloembergen N, Morgan LO (1961) Proton relaxation times in paramagnetic solutions. effects of electron spin relaxation. Chem Phys 34(3):842–850Google Scholar
  105. 105.
    Solomon I (1955) Relaxation processes in a system of two Spins. Phys Rev 99(2):559–565CrossRefGoogle Scholar
  106. 106.
    Solomon I, Bloembergen N (1956) Nuclear magnetic interactions in the HF molecule. Chem Phys 25(2):261–266Google Scholar
  107. 107.
    Merbach AE, Toth E (eds) (2001) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, New YorkGoogle Scholar
  108. 108.
    Zheng J, Zhu G, Li Y, Li C, You M, Chen T, Song E, Yang R, Tan W (2013) A spherical nucleic acid platform based on self-assembled DNA biopolymer for high-performance cancer therapy. ACS Nano 7(8):6545–6554PubMedCentralPubMedCrossRefGoogle Scholar
  109. 109.
    Girvan AC, Teng Y, Casson LK, Thomas SD, Juliger S, Ball MW, Klein JB, Pierce WM Jr, Barve SS, Bates PJ (2006) AGRO100 inhibits activation of nuclear factor-kappaB (NF-kappaB) by forming a complex with NF-kappaB essential modulator (NEMO) and nucleolin. Mol Cancer Ther 5(7):1790–1799PubMedCrossRefGoogle Scholar
  110. 110.
    Hwang DW, Ko HY, Lee JH, Kang H, Ryu SH, Song IC, Lee DS, Kim S (2010) A nucleolin-targeted multimodal nanoparticle imaging probe for tracking cancer cells using an aptamer. J Nucl Med 51(1):98–105CrossRefGoogle Scholar
  111. 111.
    Wang K, You M, Chen Y, Han D, Zhu Z, Huang J, Williams K, Yang CJ, Tan W (2011) Self-assembly of a bifunctional DNA carrier for drug delivery. Angew Chem Int Ed 50(27):6098–6101CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Stacey N. Barnaby
    • 1
    • 2
  • Timothy L. Sita
    • 2
    • 3
  • Sarah Hurst Petrosko
    • 1
    • 2
  • Alexander H. Stegh
    • 2
    • 4
  • Chad A. Mirkin
    • 1
    • 2
    • 3
  1. 1.Department of ChemistryNorthwestern UniversityEvanstonUSA
  2. 2.International Institute for NanotechnologyNorthwestern UniversityEvanstonUSA
  3. 3.Interdepartmental Biological Sciences ProgramNorthwestern UniversityEvanstonUSA
  4. 4.Ken and Ruth Davee Department of Neurology, The Northwestern Brain Tumor Institute, the Robert H. Lurie Comprehensive Cancer CenterNorthwestern UniversityChicagoUSA

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