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Journal of Drug Delivery
Volume 2017 (2017), Article ID 6971297, 22 pages
https://doi.org/10.1155/2017/6971297
Review Article

Targeted Delivery of siRNA Therapeutics to Malignant Tumors

1Department of Pathology, University of Maryland School of Medicine, 10 S. Pine St., Baltimore, MD 21201, USA
2Aparna Biosciences Corporation, 9119 Gaither Rd., Gaithersburg, MD 20877, USA

Correspondence should be addressed to A. James Mixson; ude.dnalyramu@nosxima

Received 31 August 2017; Accepted 10 October 2017; Published 9 November 2017

Academic Editor: Ambikanandan Misra

Copyright © 2017 Qixin Leng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. H. Kobayashi, R. Watanabe, and P. L. Choyke, “Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target?” Theranostics, vol. 4, no. 1, pp. 81–89, 2014. View at Publisher · View at Google Scholar · View at Scopus
  2. H. Maeda, “Nitroglycerin enhances vascular blood flow and drug delivery in hypoxic tumor tissues: Analogy between angina pectoris and solid tumors and enhancement of the EPR effect,” Journal of Controlled Release, vol. 142, no. 3, pp. 296–298, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Maeda, “Tumor-selective delivery of macromolecular drugs via the EPR effect: Background and future prospects,” Bioconjugate Chemistry, vol. 21, no. 5, pp. 797–802, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Mehvar, M. A. Robinson, and J. M. Reynolds, “Dose dependency of the kinetics of dextrans in rats: Effects of molecular weight,” Journal of Pharmaceutical Sciences, vol. 84, no. 7, pp. 815–818, 1995. View at Publisher · View at Google Scholar · View at Scopus
  5. D. W. Bartlett, H. Su, I. J. Hildebrandt, W. A. Weber, and M. E. Davis, “Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 104, no. 39, pp. 15549–15554, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. L. Deng, Y. Zhang, L. Ma et al., “Comparison of anti-EGFR-Fab conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells,” International Journal of Nanomedicine, vol. 8, pp. 3271–3283, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Laakkonen, K. Porkka, J. A. Hoffman, and E. Ruoslahti, “A tumor-homing peptide with a targeting specificity related to lymphatic vessels,” Nature Medicine, vol. 8, no. 7, pp. 751–755, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Pasqualini, E. Koivunen, R. Kain et al., “Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis,” Cancer Research, vol. 60, pp. 722–727, 2000. View at Google Scholar
  9. R. Pasqualini, E. Koivunen, and E. Ruoslahti, “|[alpha]| v Integrins as receptors for tumor targeting by circulating ligands,” Nature Biotechnology, vol. 15, no. 6, pp. 542–546, 1997. View at Publisher · View at Google Scholar
  10. Y. Ren, H. W. Cheung, G. Von Maltzhan et al., “Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4,” Science Translational Medicine, vol. 4, no. 147, Article ID 147ra112, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. N. Oku, T. Asai, K. Watanabe et al., “Anti-neovascular therapy using novel peptides homing to angiogenic vessels,” Oncogene, vol. 21, no. 17, pp. 2662–2669, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Roth, L. Agemy, V. R. Kotamraju et al., “Transtumoral targeting enabled by a novel neuropilin-binding peptide,” Oncogene, vol. 31, no. 33, pp. 3754–3763, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. E. Ruoslahti, S. N. Bhatia, and M. J. Sailor, “Targeting of drugs and nanoparticles to tumors,” The Journal of Cell Biology, vol. 188, no. 6, pp. 759–768, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. K. N. Sugahara, T. Teesalu, P. Prakash Karmali et al., “Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs,” Science, vol. 328, no. 5981, pp. 1031–1035, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Teesalu, K. N. Sugahara, V. R. Kotamraju, and E. Ruoslahti, “C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 106, no. 38, pp. 16157–16162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Teesalu, K. N. Sugahara, and E. Ruoslahti, “Tumor-penetrating peptides,” Frontiers in Oncology, vol. 3, Article ID 00216, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Babae, M. Bourajjaj, Y. Liu et al., “Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma,” Oncotarget , vol. 5, no. 16, pp. 6687–6700, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. J. D. Hood, R. Frausto, W. B. Kiosses, M. A. Schwartz, and D. A. Cheresh, “Differential αv integrin-mediated Ras-ERK signaling during two pathways of angiogenesis,” The Journal of Cell Biology, vol. 162, no. 5, pp. 933–943, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Gurrath, G. Muller, H. Kessler, M. Aumailley, and R. Timpl, “Conformation/activity studies of rationally designed potent anti-adhesive RGD peptides,” European Journal of Biochemistry, vol. 210, pp. 911–921, 1992. View at Google Scholar
  20. R. Allman, P. Cowburn, and M. Mason, “In vitro and in vivo effects of a cyclic peptide with affinity for the αvβ3 integrin in human melanoma cells,” European Journal of Cancer, vol. 36, no. 3, pp. 410–422, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. J. D. Hood, M. Bednarski, R. Frausto et al., “Tumor regression by targeted gene delivery to the neovasculature,” Science, vol. 296, no. 5577, pp. 2404–2407, 2002. View at Publisher · View at Google Scholar · View at Scopus
  22. R. M. Schiffelers, A. Ansari, J. Xu et al., “Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle,” Nucleic Acids Research, vol. 32, p. e149, 2004. View at Google Scholar
  23. H. D. Han, L. S. Mangala, J. W. Lee et al., “Targeted gene silencing using RGD-labeled chitosan nanoparticles,” Clinical Cancer Research, vol. 16, no. 15, pp. 3910–3922, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. S.-T. Chou, Q. Leng, P. Scaria, M. Woodle, and A. J. Mixson, “Selective modification of HK peptides enhances siRNA silencing of tumor targets in vivo,” Cancer Gene Therapy, vol. 18, no. 10, pp. 707–716, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. S.-T. Chou, K. Hom, D. Zhang et al., “Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds,” Biomaterials, vol. 35, no. 2, pp. 846–855, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Li, Z. Hu, H. Yin et al., “A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for "smart" small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells,” International Journal of Nanomedicine, vol. 8, pp. 1293–1306, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. R. J. Christie, Y. Matsumoto, K. Miyata et al., “Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection,” ACS Nano, vol. 6, no. 6, pp. 5174–5189, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. Y.-H. Li, Q.-S. Shi, J. Du et al., “Targeted delivery of biodegradable nanoparticles with ultrasound-targeted microbubble destruction-mediated hVEGF-siRNA transfection in human PC-3 cells in vitro,” International Journal of Molecular Medicine, vol. 31, no. 1, pp. 163–171, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. S.-T. Chou, Q. Leng, P. Scaria et al., “Surface-modified HK:siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition,” Biomacromolecules, vol. 14, no. 3, pp. 752–760, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Koide, T. Asai, K. Furuya et al., “Inhibition of Akt (ser473) phosphorylation and rapamycin-resistant cell growth by knockdown of mammalian target of rapamycin with small interfering RNA in vascular endothelial growth factor receptor-1-targeting vector,” Biological & Pharmaceutical Bulletin, vol. 34, no. 5, pp. 602–608, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. Y. Wang, P. Liu, Y. Duan et al., “Specific cell targeting with APRPG conjugated PEG-PLGA nanoparticles for treating ovarian cancer,” Biomaterials, vol. 35, no. 3, pp. 983–992, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. N. Maeda, Y. Takeuchi, M. Takada, Y. Sadzuka, Y. Namba, and N. Oku, “Anti-neovascular therapy by use of tumor neovasculature-targeted long-circulating liposome,” Journal of Controlled Release, vol. 100, no. 1, pp. 41–52, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. Y. Katanasaka, T. Ida, T. Asai, N. Maeda, and N. Oku, “Effective delivery of an angiogenesis inhibitor by neovessel-targeted liposomes,” International Journal of Pharmaceutics, vol. 360, no. 1-2, pp. 219–224, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. Z. X. Lu, L. T. Liu, and X. R. Qi, “Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy,” International Journal of Nanomedicine, vol. 6, pp. 1661–1673, 2011. View at Google Scholar
  35. H. Koide, T. Asai, H. Kato et al., “Susceptibility of PTEN-positive metastatic tumors to small interfering RNA targeting the mammalian target of rapamycin,” Nanomedicine: Nanotechnology, Biology and Medicine, vol. 11, no. 1, pp. 185–194, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Ando, T. Asai, H. Koide et al., “Advanced cancer therapy by integrative antitumor actions via systemic administration of miR-499,” Journal of Controlled Release, vol. 181, no. 1, pp. 32–39, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. A. H. Negussie, J. L. Miller, G. Reddy, S. K. Drake, B. J. Wood, and M. R. Dreher, “Synthesis and in vitro evaluation of cyclic NGR peptide targeted thermally sensitive liposome,” Journal of Controlled Release, vol. 143, no. 2, pp. 265–273, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Chen, J. J. Wu, and L. Huang, “Nanoparticles targeted with NGR motif deliver c-myc siRNA and doxorubicin for anticancer therapy,” Molecular Therapy, vol. 18, no. 4, pp. 828–834, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. K. Porkka, P. Laakkonen, J. A. Hoffman, M. Bernasconi, and E. Ruoslahti, “A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 99, no. 11, pp. 7444–7449, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. S. Christian, J. Pilch, M. E. Akerman, K. Porkka, P. Laakkonen, and E. Ruoslahti, “Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels,” The Journal of Cell Biology, vol. 163, no. 4, pp. 871–878, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. L. C. Gomes-Da-Silva, A. O. Santos, L. M. Bimbo et al., “Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment,” International Journal of Pharmaceutics, vol. 434, no. 1-2, pp. 9–19, 2012. View at Publisher · View at Google Scholar · View at Scopus
  42. L. C. Gomes-Da-Silva, J. S. Ramalho, M. C. Pedroso De Lima, S. Simões, and J. N. Moreira, “Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of both cancer and endothelial cells,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 85, no. 3, pp. 356–364, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Elsabahy, R. Shrestha, C. Clark, S. Taylor, J. Leonard, and K. L. Wooley, “Multifunctional hierarchically assembled nanostructures as complex stage-wise dual-delivery systems for coincidental yet differential trafficking of siRNA and paclitaxel,” Nano Letters, vol. 13, no. 5, pp. 2172–2181, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Numata, M. R. Reagan, R. H. Goldstein, M. Rosenblatt, and D. L. Kaplan, “Spider silk-based gene carriers for tumor cell-specific delivery,” Bioconjugate Chemistry, vol. 22, no. 8, pp. 1605–1610, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. L. Agemy, V. R. Kotamraju, D. Friedmann-Morvinski, S. Sharma, K. N. Sugahara, and E. Ruoslahti, “Proapoptotic peptide-mediated cancer therapy targeted to cell surface p32,” Molecular Therapy, vol. 21, no. 12, pp. 2195–2204, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. K. N. Sugahara, T. Teesalu, P. P. Karmali et al., “Tissue-penetrating delivery of compounds and nanoparticles into tumors,” Cancer Cell, vol. 16, no. 6, pp. 510–520, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. L. Alberici, L. Roth, K. N. Sugahara et al., “De Novo design of a tumor-penetrating peptide,” Cancer Research, vol. 73, no. 2, pp. 804–812, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. H.-B. Pang, G. B. Braun, T. Friman et al., “An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability,” Nature Communications, vol. 5, article no. 4904, 2014. View at Publisher · View at Google Scholar · View at Scopus
  49. Q. Hu, X. Gao, T. Kang et al., “CGKRK-modified nanoparticles for dual-targeting drug delivery to tumor cells and angiogenic blood vessels,” Biomaterials, vol. 34, no. 37, pp. 9496–9508, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Miao, M. Jiang, Z. Liu et al., “Co-administration of dual-targeting nanoparticles with penetration enhancement peptide for antiglioblastoma therapy,” Molecular Pharmaceutics, vol. 11, no. 1, pp. 90–101, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Shen, Q. Meng, H. Sui et al., “IRGD conjugated TPGS mediates codelivery of paclitaxel and survivin shRNA for the reversal of lung cancer resistance,” Molecular Pharmaceutics, vol. 11, no. 8, pp. 2579–2591, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. R. A. Walker and S. J. Day, “Transferrin receptor expression in non-malignant and malignant human breast tissue,” Journal of Pathology, vol. 148, pp. 217–224, 1986. View at Google Scholar
  53. K. Gkouvatsos, G. Papanikolaou, and K. Pantopoulos, “Regulation of iron transport and the role of transferrin,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1820, no. 3, pp. 188–202, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. Z. Yang, B. Yu, J. Zhu et al., “A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia,” Nanoscale, vol. 6, no. 16, pp. 9742–9751, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. S. H. Pun, F. Tack, N. C. Bellocq et al., “Targeted delivery of RNA-cleaving DNA enzyme (DNAzyme) to tumor tissue by transferrin-modified, cyclodextrin-based particles,” Cancer Biology and Therapy, vol. 3, pp. 641–650, 2004. View at Google Scholar
  56. Y. Liu, J. Tao, Y. Li et al., “Targeting hypoxia-inducible factor-1α with Tf-PEI-shRNA complex via transferrin receptor-mediated endocytosis inhibits melanoma growth,” Molecular Therapy, vol. 17, no. 2, pp. 269–277, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Salvati, A. S. Pitek, M. P. Monopoli et al., “Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface,” Nature Nanotechnology, vol. 8, no. 2, pp. 137–143, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Hong, S. Zhu, Y. Jiang, G. Tang, and Y. Pei, “Efficient tumor targeting of hydroxycamptothecin loaded PEGylated niosomes modified with transferrin,” Journal of Controlled Release, vol. 133, no. 2, pp. 96–102, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. D. W. Bartlett and M. E. Davis, “Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles,” Biotechnology and Bioengineering, vol. 99, no. 4, pp. 975–985, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. D. W. Bartlett and M. E. Davis, “Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging,” Nucleic Acids Research, vol. 34, no. 1, pp. 322–333, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. J. E. Zuckerman and M. E. Davis, “Clinical experiences with systemically administered siRNA-based therapeutics in cancer,” Nature Reviews Drug Discovery, vol. 14, no. 12, pp. 843–856, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. H. P. Suzie and M. E. Davis, “Development of a nonviral gene delivery vehicle for systemic application,” Bioconjugate Chemistry, vol. 13, no. 3, pp. 630–639, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. Z. R. Cohen, S. Ramishetti, N. Peshes-Yaloz et al., “Localized RNAi therapeutics of chemoresistant grade IV glioma using hyaluronan-grafted lipid-based nanoparticles,” ACS Nano, vol. 9, no. 2, pp. 1581–1591, 2015. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Almalik, P. J. Day, and N. Tirelli, “HA-coated chitosan nanoparticles for CD44-mediated nucleic acid delivery,” Macromolecular Bioscience, vol. 13, no. 12, pp. 1671–1680, 2013. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. Bin, Z. Yueying, and D. Yu, “Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery,” Oncology Reports, vol. 37, no. 2, pp. 937–944, 2017. View at Publisher · View at Google Scholar · View at Scopus
  66. Y. Liu, J. Sun, H. Lian, W. Cao, Y. Wang, and Z. He, “Folate and CD44 receptors dual-targeting hydrophobized hyaluronic acid paclitaxel-loaded polymeric micelles for overcoming multidrug resistance and improving tumor distribution,” Journal of Pharmaceutical Sciences, vol. 103, no. 5, pp. 1538–1547, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. E.-J. Kim, G. Shim, K. Kim, I. C. Kwon, Y.-K. Oh, and C.-K. Shim, “Hyaluronic acid complexed to biodegradable poly L-arginine for targeted delivery of siRNAs,” The Journal of Gene Medicine, vol. 11, no. 9, pp. 791–803, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. X. Yang, A. K. Iyer, A. Singh et al., “Cluster of differentiation 44 targeted hyaluronic acid based nanoparticles for MDR1 siRNA delivery to overcome drug resistance in ovarian cancer,” Pharmaceutical Research, 2014. View at Publisher · View at Google Scholar
  69. K.-M. Choi, M. Jang, J. H. Kim, and H. J. Ahn, “Tumor-specific delivery of siRNA using supramolecular assembly of hyaluronic acid nanoparticles and 2b RNA-binding protein/siRNA complexes,” Biomaterials, vol. 35, no. 25, pp. 7121–7132, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. S. I. Kim, D. Shin, T. H. Choi et al., “Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I,” Molecular Therapy, vol. 15, no. 6, pp. 1145–1152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. Y. Ding, W. Wang, M. Feng et al., “A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy,” Biomaterials, vol. 33, no. 34, pp. 8893–8905, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. Y. Ding, Y. Wang, J. Zhou et al., “Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis,” Biomaterials, vol. 35, no. 25, pp. 7214–7227, 2014. View at Publisher · View at Google Scholar · View at Scopus
  73. X. Li, Q. Zhao, and L. Qiu, “Smart ligand: Aptamer-mediated targeted delivery of chemotherapeutic drugs and siRNA for cancer therapy,” Journal of Controlled Release, vol. 171, no. 2, pp. 152–162, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. D. Xiang, S. Shigdar, G. Qiao et al., “Aptamer-mediated cancer gene therapy,” Current Gene Therapy, vol. 15, no. 2, pp. 109–119, 2015. View at Publisher · View at Google Scholar · View at Scopus
  75. J. E. Rosenberg, R. M. Bambury, E. M. Van Allen et al., “A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma,” Investigational New Drugs, vol. 32, no. 1, pp. 178–187, 2014. View at Publisher · View at Google Scholar · View at Scopus
  76. T. C. Chu, K. Y. Twu, A. D. Ellington, and M. Levy, “Aptamer mediated siRNA delivery,” Nucleic Acids Research, vol. 34, no. 10, article e73, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. J. O. McNamara II, E. R. Andrechek, Y. Wang et al., “Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras,” Nature Biotechnology, vol. 24, no. 8, pp. 1005–1015, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. J. P. Dassie, X.-Y. Liu, G. S. Thomas et al., “Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors,” Nature Biotechnology, vol. 27, no. 9, pp. 839–846, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. N. Subramanian, J. R. Kanwar, R. K. Kanwar et al., “EpCAM aptamer-siRNA chimera targets and regress epithelial cancer,” PLoS ONE, vol. 10, no. 7, Article ID e0132407, 2015. View at Publisher · View at Google Scholar · View at Scopus
  80. H. Y. Liu and X. Gao, “A universal protein tag for delivery of SiRNA-aptamer chimeras,” Scientific Reports, vol. 3, article 3129, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. J. Zhou and J. J. Rossi, “The therapeutic potential of cell-internalizing aptamers,” Current Topics in Medicinal Chemistry, vol. 9, no. 12, pp. 1144–1157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. N. Zhao, H. G. Bagaria, M. S. Wong, and Y. Zu, “A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma,” Journal of Nanobiotechnology, vol. 9, article no. 2, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. V. Bagalkot and X. Gao, “SiRNA-aptamer chimeras on nanoparticles: preserving targeting functionality for effective gene silencing,” ACS Nano, vol. 5, no. 10, pp. 8131–8139, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. S. E. Wilner, B. Wengerter, K. Maier et al., “An RNA alternative to human transferrin: A new tool for targeting human cells,” Molecular Therapy - Nucleic Acids, vol. 1, article no. e21, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. N. Subramanian, J. R. Kanwar, P. K. Athalya et al., “EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex,” Journal of Biomedical Science, vol. 22, no. 1, article no. 4, 2015. View at Publisher · View at Google Scholar · View at Scopus
  86. Z. Hao, W. Fan, J. Hao et al., “Efficient delivery of micro RNA to bone-metastatic prostate tumors by using aptamer-conjugated atelocollagen in vitro and in vivo,” Drug Delivery, vol. 23, no. 3, pp. 874–881, 2016. View at Publisher · View at Google Scholar · View at Scopus
  87. J. Zhou, B. Soontornworajit, J. Martin, B. A. Sullenger, E. Gilboa, and Y. Wang, “A hybrid DNA aptamer-dendrimer nanomaterial for targeted cell labeling,” Macromolecular Bioscience, vol. 9, no. 9, pp. 831–835, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. T. L. Cuellar, D. Barnes, C. Nelson et al., “Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB-siRNA conjugates,” Nucleic Acids Research, vol. 43, no. 2, pp. 1189–1203, 2015. View at Publisher · View at Google Scholar · View at Scopus
  89. Y.-D. Yao, T.-M. Sun, S.-Y. Huang et al., “Targeted delivery of PLK1-siRNA by ScFv suppresses Her2 + breast cancer growth and metastasis,” Science Translational Medicine, vol. 4, no. 130, Article ID 130ra48, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. S. Bäumer, N. Bäumer, N. Appel et al., “Antibody-mediated delivery of anti-KRAS-siRNA in vivo overcomes therapy resistance in colon cancer,” Clinical Cancer Research, vol. 21, no. 6, pp. 1383–1394, 2015. View at Publisher · View at Google Scholar · View at Scopus
  91. F. Wang, H.-R. Bai, J. Wang, Y.-Z. Bai, and C.-W. Dou, “Glioma growth inhibition in vitro and in vivo by single chain variable fragments of the transferrin receptor conjugated to survivin small interfering RNA,” Journal of International Medical Research, vol. 39, no. 5, pp. 1701–1712, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. C.-F. Xia, Y. Zhang, Y. Zhang, R. J. Boado, and W. M. Pardridge, “Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology,” Pharmaceutical Research, vol. 24, no. 12, pp. 2309–2316, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. H. Lu, D. Wang, S. Kazane et al., “Site-specific antibody-polymer conjugates for siRNA delivery,” Journal of the American Chemical Society, vol. 135, no. 37, pp. 13885–13891, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. L. Zeng, J. Li, J. Li et al., “Effective suppression of the kirsten rat sarcoma viral oncogene in pancreatic tumor cells via targeted small interfering rna delivery using nanoparticles,” Pancreas, vol. 44, no. 2, pp. 250–259, 2015. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Dou, X.-Z. Yang, M.-H. Xiong et al., “ScFv-Decorated PEG-PLA-Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer,” Advanced Healthcare Materials, vol. 3, no. 11, pp. 1792–1803, 2014. View at Publisher · View at Google Scholar · View at Scopus
  96. D. P. Y. Chan, G. F. Deleavey, S. C. Owen, M. J. Damha, and M. S. Shoichet, “Click conjugated polymeric immuno-nanoparticles for targeted siRNA and antisense oligonucleotide delivery,” Biomaterials, vol. 34, no. 33, pp. 8408–8415, 2013. View at Publisher · View at Google Scholar · View at Scopus
  97. Y. Wang, P. Liu, J. Du, Y. Sun, F. Li, and Y. Duan, “Targeted siRNA delivery by anti-HER2 antibody-modified nanoparticles of mPEG-chitosan diblock copolymer,” Journal of Biomaterials Science, Polymer Edition, vol. 24, no. 10, pp. 1219–1232, 2013. View at Publisher · View at Google Scholar · View at Scopus
  98. A. Okamoto, T. Asai, H. Kato et al., “Antibody-modified lipid nanoparticles for selective delivery of siRNA to tumors expressing membrane-anchored form of HB-EGF,” Biochemical and Biophysical Research Communications, vol. 449, no. 4, pp. 460–465, 2014. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Höbel, D. Vornicescu, M. Bauer, D. Fischer, M. Keusgen, and A. Aigner, “A novel method for the assessment of targeted PEI-based nanoparticle binding based on a static surface plasmon resonance system,” Analytical Chemistry, vol. 86, no. 14, pp. 6827–6835, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Mitra, M. Kandalam, J. Rangasamy et al., “Novel epithelial cell adhesion molecule antibody conjugated polyethyleneimine-capped gold nanoparticles for enhanced and targeted small interfering RNA delivery to retinoblastoma cells,” Molecular Vision, vol. 19, pp. 1029–1038, 2013. View at Google Scholar · View at Scopus
  101. M. Shen, F. Gong, P. Pang et al., “An MRI-visible non-viral vector for targeted Bcl-2 siRNA delivery to neuroblastoma,” International Journal of Nanomedicine, vol. 7, pp. 3319–3332, 2012. View at Publisher · View at Google Scholar · View at Scopus
  102. E. Bourseau-Guilmain, J. Béjaud, A. Griveau et al., “Development and characterization of immuno-nanocarriers targeting the cancer stem cell marker AC133,” International Journal of Pharmaceutics, vol. 423, no. 1, pp. 93–101, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. A. E. Felber, B. Castagner, M. Elsabahy, G. F. Deleavey, M. J. Damha, and J.-C. Leroux, “SiRNA nanocarriers based on methacrylic acid copolymers,” Journal of Controlled Release, vol. 152, no. 1, pp. 159–167, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. Y. Chen, X. Zhu, X. Zhang, B. Liu, and L. Huang, “Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy,” Molecular Therapy, vol. 18, no. 9, pp. 1650–1656, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. J. Zhao, Y. Mi, and S.-S. Feng, “Targeted co-delivery of docetaxel and siPlk1 by herceptin-conjugated vitamin E TPGS based immunomicelles,” Biomaterials, vol. 34, no. 13, pp. 3411–3421, 2013. View at Publisher · View at Google Scholar · View at Scopus
  106. W. M. Pardridge, “shRNA and siRNA delivery to the brain,” Advanced Drug Delivery Reviews, vol. 59, no. 2-3, pp. 141–152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. T. Yoshizawa, Y. Hattori, M. Hakoshima, K. Koga, and Y. Maitani, “Folate-linked lipid-based nanoparticles for synthetic siRNA delivery in KB tumor xenografts,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 70, no. 3, pp. 718–725, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. J. S. Kim, M. H. Oh, J. Y. Park, T. G. Park, and Y. S. Nam, “Protein-resistant, reductively dissociable polyplexes for in vivo systemic delivery and tumor-targeting of siRNA,” Biomaterials, vol. 34, no. 9, pp. 2370–2379, 2013. View at Publisher · View at Google Scholar · View at Scopus
  109. J.-M. Li, Y.-Y. Wang, W. Zhang, H. Su, L.-N. Ji, and Z.-W. Mao, “Low-weight polyethylenimine cross-linked 2-hydroxypopyl-β-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA,” International Journal of Nanomedicine, vol. 8, pp. 2101–2117, 2013. View at Publisher · View at Google Scholar · View at Scopus
  110. L. Novo, K. M. Takeda, T. Petteta et al., “Targeted decationized polyplexes for siRNA delivery,” Molecular Pharmaceutics, vol. 12, no. 1, pp. 150–161, 2015. View at Publisher · View at Google Scholar · View at Scopus
  111. D. Dong, W. Gao, Y. Liu, and X.-R. Qi, “Therapeutic potential of targeted multifunctional nanocomplex co-delivery of siRNA and low-dose doxorubicin in breast cancer,” Cancer Letters, vol. 359, no. 2, pp. 178–186, 2015. View at Publisher · View at Google Scholar · View at Scopus
  112. S.-Y. Lin, W.-Y. Zhao, H.-C. Tsai, W.-H. Hsu, C.-L. Lo, and G.-H. Hsiue, “Sterically polymer-based liposomal complexes with dual-shell structure for enhancing the siRNA delivery,” Biomacromolecules, vol. 13, no. 3, pp. 664–675, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. H. Li, M. Miteva, K. C. Kirkbride et al., “Dual MMP7-proximity-activated and folate receptor-targeted nanoparticles for siRNA delivery,” Biomacromolecules, vol. 16, no. 1, pp. 192–201, 2015. View at Publisher · View at Google Scholar · View at Scopus
  114. L. De Backer, K. Braeckmans, M. C. A. Stuart, J. Demeester, S. C. De Smedt, and K. Raemdonck, “Bio-inspired pulmonary surfactant-modified nanogels: A promising siRNA delivery system,” Journal of Controlled Release, vol. 206, pp. 177–186, 2015. View at Publisher · View at Google Scholar · View at Scopus
  115. T. J. Lee, F. Haque, D. Shu et al., “RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model,” Oncotarget , vol. 6, no. 17, pp. 14766–14776, 2015. View at Publisher · View at Google Scholar · View at Scopus
  116. C. Dohmen, D. Edinger, T. Fröhlich et al., “Nanosized multifunctional polyplexes for receptor-mediated SiRNA delivery,” ACS Nano, vol. 6, no. 6, pp. 5198–5208, 2012. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Krais, L. Wortmann, L. Hermanns et al., “Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum,” Nanomedicine: Nanotechnology, Biology and Medicine, vol. 10, no. 7, pp. 1421–1431, 2014. View at Publisher · View at Google Scholar · View at Scopus
  118. X. Ma, Y. Zhao, K. W. Ng, and Y. Zhao, “Integrated hollow mesoporous silica nanoparticles for target drug/siRNA co-delivery,” Chemistry - A European Journal, vol. 19, no. 46, pp. 15593–15603, 2013. View at Publisher · View at Google Scholar · View at Scopus
  119. H. Lee, A. K. R. Lytton-Jean, and Y. Chen, “Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery,” Nature Nanotechnology, vol. 7, no. 6, pp. 389–393, 2012. View at Publisher · View at Google Scholar · View at Scopus
  120. D.-J. Lee, E. Kessel, D. Edinger et al., “Dual antitumoral potency of EG5 siRNA nanoplexes armed with cytotoxic bifunctional glutamyl-methotrexate targeting ligand,” Biomaterials, vol. 77, pp. 98–110, 2016. View at Publisher · View at Google Scholar · View at Scopus
  121. D. J. O'Shannessy, G. Yu, R. Smale et al., “Folate receptor alpha expression in lung cancer: diagnostic and prognostic significance,” Oncotarget , vol. 3, no. 4, pp. 414–425, 2012. View at Publisher · View at Google Scholar · View at Scopus
  122. N. Parker, M. J. Turk, E. Westrick, J. D. Lewis, P. S. Low, and C. P. Leamon, “Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay,” Analytical Biochemistry, vol. 338, no. 2, pp. 284–293, 2005. View at Publisher · View at Google Scholar · View at Scopus
  123. S.-D. Li, S. Chono, and L. Huang, “Efficient gene silencing in metastatic tumor by siRNA formulated in surface-modified nanoparticles,” Journal of Controlled Release, vol. 126, no. 1, pp. 77–84, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. J. Li, Y. Yang, and L. Huang, “Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor,” Journal of Controlled Release, vol. 158, no. 1, pp. 108–114, 2012. View at Publisher · View at Google Scholar · View at Scopus
  125. Y. Yang, Y. Hu, Y. Wang, J. Li, F. Liu, and L. Huang, “Nanoparticle delivery of pooled siRNA for effective treatment of non-small cell lung caner,” Molecular Pharmaceutics, vol. 9, no. 8, pp. 2280–2289, 2012. View at Publisher · View at Google Scholar · View at Scopus
  126. W.-H. Chen, R. L. G. Lecaros, Y.-C. Tseng, L. Huang, and Y.-C. Hsu, “Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer,” Cancer Letters, vol. 359, no. 1, pp. 65–74, 2015. View at Publisher · View at Google Scholar · View at Scopus
  127. J. Guo, J. R. Ogier, S. Desgranges, R. Darcy, and C. ODriscoll, “Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice,” Biomaterials, vol. 33, no. 31, pp. 7775–7784, 2012. View at Publisher · View at Google Scholar · View at Scopus
  128. G. Gregoriadis and J. Senior, “Targeting of small unilamellar liposomes to the galactose receptor in vivo,” Biochemical Society Transactions, vol. 12, no. 2, pp. 337–339, 1984. View at Publisher · View at Google Scholar · View at Scopus
  129. I. K. Park, Y. H. Park, B. A. Shin et al., “Galactosylated chitosan-graft-dextran as hepatocyte-targeting DNA carrier,” Journal of Controlled Release, vol. 69, pp. 97–108, 2000. View at Google Scholar
  130. L. Han, C. Tang, and C. Yin, “Dual-targeting and pH/redox-responsive multi-layered nanocomplexes for smart co-delivery of doxorubicin and siRNA,” Biomaterials, vol. 60, pp. 42–52, 2015. View at Publisher · View at Google Scholar · View at Scopus
  131. L. Han, C. Tang, and C. Yin, “Oral delivery of shRNA and siRNA via multifunctional polymeric nanoparticles for synergistic cancer therapy,” Biomaterials, vol. 35, no. 15, pp. 4589–4600, 2014. View at Publisher · View at Google Scholar · View at Scopus
  132. J. H. Lee, J. A. Engler, J. F. Collawn, and B. A. Moore, “Receptor mediated uptake of peptides that bind the human transferrin receptor,” European Journal of Biochemistry, vol. 268, no. 7, pp. 2004–2012, 2001. View at Publisher · View at Google Scholar · View at Scopus
  133. S. Oh, B. J. Kim, N. P. Singh, H. Lai, and T. Sasaki, “Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide,” Cancer Letters, vol. 274, no. 1, pp. 33–39, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. L.-Y. Gao, X.-Y. Liu, C.-J. Chen et al., “Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for invivo siRNA delivery,” Biomaterials, vol. 35, no. 6, pp. 2066–2078, 2014. View at Publisher · View at Google Scholar · View at Scopus
  135. L. Zhu, F. Perche, T. Wang, and V. P. Torchilin, “Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs,” Biomaterials, vol. 35, no. 13, pp. 4213–4222, 2014. View at Publisher · View at Google Scholar · View at Scopus
  136. M. Malhotra, C. Tomaro-Duchesneau, S. Saha, and S. Prakash, “Systemic siRNA delivery via peptide-tagged polymeric nanoparticles, targeting PLK1 gene in a mouse xenograft model of colorectal cancer,” International Journal of Biomaterials, vol. 2013, Article ID 252531, 2013. View at Publisher · View at Google Scholar · View at Scopus
  137. S. Hong, X. Zhang, J. Chen, J. Zhou, Y. Zheng, and C. Xu, “Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro,” Journal of Ovarian Research, vol. 6, no. 1, article no. 80, 2013. View at Publisher · View at Google Scholar · View at Scopus
  138. X.-Y. Zhang, J. Chen, Y.-F. Zheng et al., “Follicle-stimulating hormone peptide can facilitate paclitaxel nanoparticles to target ovarian carcinoma in vivo,” Cancer Research, vol. 69, no. 16, pp. 6506–6514, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. V. Shah, O. Taratula, O. B. Garbuzenko, O. R. Taratula, L. Rodriguez-Rodriguez, and T. Minko, “Targeted nanomedicine for suppression of CD44 and simultaneous cell death induction in ovarian cancer: An optimal delivery of siRNA and anticancer drug,” Clinical Cancer Research, vol. 19, no. 22, pp. 6193–6204, 2013. View at Publisher · View at Google Scholar · View at Scopus
  140. M. Sioud and A. Mobergslien, “Efficient siRNA targeted delivery into cancer cells by gastrin-releasing peptides,” Bioconjugate Chemistry, vol. 23, no. 5, pp. 1040–1049, 2012. View at Publisher · View at Google Scholar · View at Scopus
  141. Y. Gao, Z.-Y. Wang, J. Zhang et al., “RVG-peptide-linked trimethylated chitosan for delivery of siRNA to the brain,” Biomacromolecules, vol. 15, no. 3, pp. 1010–1018, 2014. View at Publisher · View at Google Scholar · View at Scopus
  142. M. Gooding, M. Malhotra, D. J. McCarthy et al., “Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: In vitro analysis,” European Journal of Pharmaceutical Sciences, vol. 71, pp. 80–92, 2015. View at Publisher · View at Google Scholar · View at Scopus
  143. L. Yang, H. K. Sajja, Z. Cao et al., “uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection,” Theranostics, vol. 4, no. 1, pp. 106–118, 2014. View at Publisher · View at Google Scholar · View at Scopus
  144. A. van Waarde, A. A. Rybczynska, N. K. Ramakrishnan, K. Ishiwata, P. H. Elsinga, and R. A. J. O. Dierckx, “Potential applications for sigma receptor ligands in cancer diagnosis and therapy,” Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1848, no. 10, pp. 2703–2714, 2015. View at Publisher · View at Google Scholar · View at Scopus
  145. K. F. Pirollo, G. Zon, A. Rait et al., “Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery,” Human Gene Therapy, vol. 17, no. 1, pp. 117–124, 2006. View at Publisher · View at Google Scholar · View at Scopus
  146. Y. Chen, W. Wang, G. Lian et al., “Development of an MRI-visible nonviral vector for siRNA delivery targeting gastric cancer,” International Journal of Nanomedicine, vol. 7, pp. 359–368, 2012. View at Google Scholar
  147. W. Alshaer, H. Hillaireau, J. Vergnaud, S. Ismail, and E. Fattal, “Functionalizing Liposomes with anti-CD44 Aptamer for Selective Targeting of Cancer Cells,” Bioconjugate Chemistry, vol. 26, no. 7, pp. 1307–1313, 2015. View at Publisher · View at Google Scholar · View at Scopus
  148. D. Sánchez-Martín, Á. M. Cuesta, V. Fogal, E. Ruoslahti, and L. Álvarez-Vallina, “The multicompartmental p32/gClqR as a new target for antibody-based tumor targeting strategies,” The Journal of Biological Chemistry, vol. 286, no. 7, pp. 5197–5203, 2011. View at Publisher · View at Google Scholar · View at Scopus
  149. K. Pu, L. Yuan, L. Chen et al., “Identification of VEGFR2-binding peptides using high throughput bacterial display methods and functional assessment,” Current Cancer Drug Targets, vol. 15, no. 2, pp. 158–170, 2015. View at Publisher · View at Google Scholar · View at Scopus
  150. B. Kim, J. Yang, M. Hwang et al., “Aptamer-modified magnetic nanoprobe for molecular MR imaging of VEGFR2 on angiogenic vasculature,” Nanoscale Research Letters, vol. 8, no. 1, pp. 1–10, 2013. View at Publisher · View at Google Scholar · View at Scopus