Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an un questioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Iso lated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed.
KeywordsLymphomaNucleic Acid AptamerSELEXCell-Type Specific Drug DeliveryBiosensorNanotechnology
N. Bakshi and I. Maghfoor, “The Current Lymphoma Classification: New Concepts and Practical Applications Triumphs and Woes,” Annals of Saudi Medicine, Vol. 32. No. 3, 2012, pp. 296-305.
J. W. Sweetenham, “Lymphoblastic Lymphoma in Adults,” Current Hematologic Malignancy Reports, Vol. 1. No. 4, 2006, pp. 241-247. doi:10.1007/s11899-006-0005-8
S. Ogino, C. S. Fuchs and E. Giovannucci, “How Many Molecular Subtypes? Implications of the Unique Tumor Principle in Personalized Medicine,” Expert Review of Molecular Diagnostics, Vol. 12. No. 6, 2012, pp. 621-628. doi:10.1586/erm.12.46
K. R. Shankland, J. O. Armitage and B. W. Hancock, “Non-Hodgkin Lymphoma,” Lancet, Vol. 380. No. 9844, 2012, pp. 848-857. doi:10.1016/S0140-6736(12)60605-9
R. Kuppers, “New Insights in the Biology of Hodgkin Lymphoma,” Hematology/The Education Program of the American Society of Hematology American Society of Hematology Education Program, Vol. 2012, 2012, pp. 328-334.
R. Kuppers, A. Engert and M. L. Hansmann, “Hodgkin Lymphoma,” The Journal of Clinical Investigation, Vol. 122. No. 10, 2012, pp. 3439-3447. doi:10.1172/JCI61245
J. Zhou and J. J. Rossi, “Aptamer-Targeted Cell-Specific RNA Interference,” Silence, Vol. 1, No. 1, 2010, p. 4. doi:10.1186/1758-907X-1-4
J. Zhou and J. J. Rossi, “The Therapeutic Potential of Cell-Internalizing Aptamers,” Current topics in Medicinal Chemistry, Vol. 9. No. 12, 2009, pp. 1144-1157. doi:10.2174/156802609789630893
J. Zhou and J. J. Rossi, “Bivalent Aptamers Deliver the Punch,” Chemistry & Biology, Vol. 15. No. 7, 2008, pp. 644-645. doi:10.1016/j.chembiol.2008.07.004
X. Ni, M. Castanares, A. Mukherjee and S. E. Lupold, “Nucleic Acid Aptamers: Clinical Applications and Promising New Horizons,” Current Medicinal Chemistry, Vol. 18, No. 27, 2011, pp. 4206-4214. doi:10.2174/092986711797189600
A. D. Ellington and J. W. Szostak, “In Vitro Selection of RNA Molecules that Bind Specific Ligands,” Nature, Vol. 346, No. 6287, 1990, pp. 818-822. doi:10.1038/346818a0
W. O. Tucker, K. T. Shum and J. A. Tanner, “G-Quadruplex DNA Aptamers and Their Ligands: Structure, Function and Application,” Current Pharmaceutical Design, Vol. 18, No. 14, 2012, pp. 2014-2026. doi:10.2174/138161212799958477
J. Liu, M. You, Y. Pu, H. Liu, M. Ye and W. Tan, “Recent Developments in Protein and Cell-Targeted Aptamer Selection and Applications,” Current Medicinal Chemistry, Vol. 18, No. 27, 2011, pp. 4117-4125. doi:10.2174/092986711797189619
Y. Nakamura, A. Ishiguro and S. Miyakawa, “RNA Plasticity and Selectivity Applicable to Therapeutics and Novel Biosensor Development,” Genes to Cells: Devoted to Molecular & Cellular Mechanisms, Vol. 17, No. 5, 2012, pp. 344-364. doi:10.1111/j.1365-2443.2012.01596.x
S. D. Jayasena, “Aptamers: An Emerging Class of Molecules that Rival Antibodies in Diagnostics,” Clinical Chemistry, Vol. 45, No. 9, 1999, pp. 1628-1650.
E. W. Ng, D. T. Shima, P. Calias, E. T. Cunningham, Jr., D. R. Guyer and A. P. Adamis, “Pegaptanib, a Targeted anti-VEGF Aptamer for Ocular Vascular Disease,” Nature Reviews Drug Discovery, Vol. 5, No. 2, 2006, pp. 123-132. doi:10.1038/nrd1955
E. W. Ng and A. P. Adamis, “Anti-VEGF Aptamer (Pegaptanib) Therapy for Ocular Vascular Diseases,” Annals of the New York Academy of Sciences, Vol. 1082, 2006, pp. 151-171. doi:10.1196/annals.1348.062
G. Zhu, M. Ye, M. J. Donovan, E. Song, Z. Zhao and W. Tan, “Nucleic Acid Aptamers: An Emerging Frontier in Cancer Therapy,” Chemical Communications (Camb), Vol. 48, No. 85, 2012, pp. 10472-10480. doi:10.1039/c2cc35042d
Y. Zhang, H. Hong and W. Cai, “Tumor-Targeted Drug Delivery with Aptamers,” Current Medicinal Chemistry, Vol. 18, No. 27, 2011, pp. 4185-4194. doi:10.2174/092986711797189547
A. S. Barbas, J. Mi, B. M. Clary and R. R. White, “Aptamer Applications for Targeted Cancer Therapy,” Future Oncology, Vol. 6, No. 7, 2010, pp. 1117-1126. doi:10.2217/fon.10.67
J. Zhou and J. J. Rossi, “Cell-Specific Aptamer-Mediated Targeted Drug Delivery,” Oligonucleotides, Vol. 21, No. 1, 2011, pp. 1-10. doi:10.1089/oli.2010.0264
C. Tuerk and L. Gold, “Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase,” Science, Vol. 249, No. 4968, 1990, pp. 505-510. doi:10.1126/science.2200121
P. Dua, S. Kim and D. K. Lee, “Nucleic Acid Aptamers Targeting Cell-Surface Proteins,” Methods, Vol. 54, No. 2, 2011, pp. 215-225. doi:10.1016/j.ymeth.2011.02.002
S. P. Ho, D. H. Britton, B. A. Stone, D. L. Behrens, L. M. Leffet, F. W. Hobbs, et al., “Potent Antisense Oligonucleotides to the Human Multidrug Resistance-1 mRNA Are Rationally Selected by Mapping RNA-Accessible Sites with Oligonucleotide Libraries,” Nucleic Acids Research, Vol. 24. No. 10, 1996, pp. 1901-1907. doi:10.1093/nar/24.10.1901
R. V. Talanian, C. J. McKnight, R. Rutkowski and P. S. Kim, “Minimum Length of a Sequence-Specific DNA Binding Peptide,” Biochemistry, Vol. 31, No. 30, 1992, pp. 6871-6875. doi:10.1021/bi00145a002
A. D. Keefe and S. T. Cload, “SELEX with Modified Nucleotides,” Current Opinion in Chemical Biology, Vol. 12, No. 4, 2008, pp. 448-456. doi:10.1016/j.cbpa.2008.06.028
C. Forster, M. Zydek, M. Rothkegel, Z. Wu, C. Gallin, R. Gessner, et al., “Properties of an LNA-Modified Ricin RNA Aptamer,” Biochemical and Biophysical Research Communications, Vol. 419. No. 1, 2012, pp. 60-65. doi:10.1016/j.bbrc.2012.01.127
S. Hoffmann, J. Hoos, S. Klussmann and S. Vonhoff, “RNA Aptamers and Spiegelmers: Synthesis, Purification, and Post-Synthetic PEG Conjugation,” In: S. L. Beaucage, et al., Current Protocols in Nucleic Acid Chemistry, 2011, pp. 41-30.
L. H. Lauridsen, J. A. Rothnagel and R. N. Veedu, “Enzymatic Recognition of 2'-Modified Ribonucleoside 5'-Triphosphates: Towards the Evolution of Versatile Aptamers,” Chembiochem: A European Journal of Chemical Biology, Vol. 13, No. 1, 2012, pp. 19-25. doi:10.1002/cbic.201100648
S. C. Gopinath, “Methods Developed for SELEX,” Analytical and Bioanalytical Chemistry, Vol. 387, No. 1, 2007, pp. 171-182. doi:10.1007/s00216-006-0826-2
A. V. Kulbachinskiy, “Methods for Selection of Aptamers to Protein Targets,” Biochemistry (Mosc), Vol. 72, No. 13, 2007, pp. 1505-1518. doi:10.1134/S000629790713007X
T. S. Misono and P. K. Kumar, “Selection of RNA Aptamers against Human Influenza Virus Hemagglutinin Using Surface Plasmon Resonance,” Analytical Biochemistry, Vol. 342, No. 2, 2005, pp. 312-317. doi:10.1016/j.ab.2005.04.013
K. M. Ahmad, S. S. Oh, S. Kim, F. M. McClellen, Y. Xiao and H. T. Soh, “Probing the Limits of Aptamer Affinity with a Microfluidic SELEX Platform,” PloS One, Vol. 6, No. 11, 2011, p. e27051. doi:10.1371/journal.pone.0027051
J. O. McNamara, 2nd, E. R. Andrechek, Y. Wang, K. D. Viles, R. E. Rempel, E. Gilboa, et al., “Cell Type-Specific Delivery of siRNAs with Aptamer-siRNA Chimeras,” Nature Biotechnology, Vol. 24, No. 8, 2006, pp. 1005-1015. doi:10.1038/nbt1223
J. Wang and G. Li, “Aptamers against Cell Surface Receptors: Selection, Modification and Application,” Current Medicinal Chemistry, Vol. 18. No. 27, 2011, pp. 4107-4116. doi:10.2174/09298 6711797189628
K. W. Thiel and P. H. Giangrande, “Therapeutic Applications of DNA and RNA Aptamers,” Oligonucleotides, Vol. 19, No. 3, 2009, pp. 209-222. doi:10.1089/oli.2009.0199
K. W. Thiel and P. H. Giangrande, “Intracellular Delivery of RNA-Based Therapeutics Using Aptamers,” Therapeutic Delivery, Vol. 1, No. 6, 2010, pp. 849-861. doi:10.4155/tde.10.61
M. Ye, J. Hu, M. Peng, J. Liu, H. Liu, X. Zhao, et al., “Generating Aptamers by Cell-SELEX for Applications in Molecular Medicine,” International Journal of Molecular Sciences, Vol. 13, No. 3, 2012, pp. 3341-3353. doi:10.3390/ijms13033341
K. T. Guo, A. Paul, C. Schichor, G. Ziemer and H. P. Wendel, “CELL-SELEX: Novel Perspectives of Aptamer-Based Therapeutics,” International Journal of Molecular Sciences, Vol. 9, No. 4, 2008, pp. 668-678. doi:10.3390/ijms9040668
E. M. Molyneux, R. Rochford, B. Griffin, R. Newton, G. Jackson, G. Menon, et al., “Burkitt’s Lymphoma,” The Lancet, Vol. 379, No. 9822, 2012, pp. 1234-1244. doi:10.1016/S0140-6736(11)61177-X
A. Stacchini, A. Barreca, A. Demurtas, S. Aliberti, P. F. di Celle and D. Novero, “Flow Cytometric Detection and Quantification of CD56 (Neural Cell Adhesion Molecule, NCAM) Expression in Diffuse Large B Cell Lymphomas and Review of the Literature,” Histopathology, Vol. 60, No. 3, 2012, pp. 452-459. doi:10.1111/j.1365-2559.2011.04098.x
N. J. Rawlinson, P. Baker and S. B. Kahwash, “Burkitt’s Leukemia with an Atypical Immunophenotype: Report of a Case and Review of Literature,” Laboratory Hematology: Official Publication of the International Society for Laboratory Hematology, Vol. 17, No. 4, 2011, pp. 27-31. doi:10.1532/LH96.11004
M. Bruggemann, N. Gokbuget and M. Kneba, “Acute Lymphoblastic Leukemia: Monitoring Minimal Residual Disease as a Therapeutic Principle,” Seminars in Oncology, Vol. 39, No. 1, 2012, pp. 47-57. doi:10.1053/j.seminoncol.2011.11.009
A. M. El-Sayed, M. H. El-Borai, A. A. Bahnassy and S. M. El-Gerzawi, “Flow Cytometric Immunophenotyping (FCI) of Lymphoma: Correlation with Histopathology and Immunohistochemistry,” Diagnostic pathology, Vol. 3, 2008, p. 43. doi:10.1186/1746-1596-3-43
S. H. Speck, “EBV Framed in Burkitt Lymphoma,” Nature Medicine, Vol. 8, No. 10, 2002, pp. 1086-1087.
Y. H. Kang, C. J. Park, E. J. Seo, J. Huh, S. B. Kim, Y. K. Kang, et al., “Polymerase Chain Reaction-Based Diagnosis of Bone Marrow Involvement in 170 Cases of NonHodgkin Lymphoma,” Cancer, Vol. 94, No. 12, 2002, pp. 3073-3082. doi:10.1002/cncr.10584
J. Zhou, M. R. Battig and Y. Wang, “Aptamer-Based Molecular Recognition for Biosensor Development,” Analytical and Bioanalytical Chemistry, Vol. 398, No. 6, 2010, pp. 2471-2480. doi:10.1007/s00216-010-3987-y
T. Hermann and D. J. Patel, “Adaptive Recognition by Nucleic Acid Aptamers,” Science, Vol. 287, No. 5454, 2000, pp. 820-825. doi:10.1126/science.287.5454.820
G. Campuzano-Zuluaga, M. Cioffi-Lavina, I. S. Lossos and J. R. Chapman-Fredricks, “Frequency and Extent of CD30 Expression in Diffuse Large B-Cell Lymphoma and Its Relation to Clinical and Biologic Factors: A Retrospective Study of 167 Cases,” Leukemia & Lymphoma, 2013. doi:10.3109/10428194.2013.778407
S. Hu, Z. Y. Xu-Monette, A. Balasubramanyam, G. C. Manyam, C. Visco, A. Tzankov, et al., “CD30 Expression Defines a Novel Subset of Diffuse Large B-Cell Lymphoma with Favorable Prognosis and Distinct Gene Expression Signature: A Report from the International DLBCL Rituximab-CHOP Consortium Program Study,” Blood, Vol. 121, No. 4, 2013, pp. 2715-2724. doi:10.1182/blood-2012-10-461848
S. K. Lau, P. Thomas and L. M. Weiss, “Immunohistochemical Evaluation of CON6D/B5: A New CD30 Monoclonal Antibody,” Applied Immunohistochemistry & Molecular Morphology: AIMM/Official Publication of the Society for Applied Immunohistochemistry, Vol. 18, No. 3, 2010, pp. 273-277. doi:10.1097/PAI.0b013e3181c81d31
T. Mori, A. Oguro, T. Ohtsu and Y. Nakamura, “RNA Aptamers Selected against the Receptor Activator of NF-kappaB Acquire General Affinity to Proteins of the Tumor Necrosis Factor Receptor Family,” Nucleic Acids Research, Vol. 32, No. 20, 2004, pp. 6120-6128. doi:10.1093/nar/gkh949
P. Zhang, N. Zhao, Z. Zeng, Y. Feng, C. H. Tung, C. C. Chang, et al., “Using an RNA Aptamer Probe for Flow Cytometry Detection of CD30-Expressing Lymphoma Cells,” Laboratory Investigation, Vol. 89, No. 12, 2009, pp. 1423-1432. doi:10.1038/labinvest.2009.113
Z. Zeng, P. Zhang, N. Zhao, A. M. Sheehan, C. H. Tung, C. C. Chang, et al., “Using Oligonucleotide Aptamer Probes for Immunostaining of Formalin-Fixed and Paraffin-Embedded Tissues,” Modern Pathology, Vol. 23, No. 12, 2010, pp. 1553-1558. doi:10.1038/modpathol.2010.151
J. A. Ferry, “Burkitt’s Lymphoma: Clinicopathologic Features and Differential Diagnosis,” The Oncologist, Vol. 11, No. 4, 2006, pp. 375-383. doi:10.1634/theoncologist.11-4-375
Z. Tang, D. Shangguan, K. Wang, H. Shi, K. Sefah, P. Mallikratchy, et al., “Selection of Aptamers for Molecular Recognition and Characterization of Cancer Cells,” Analytical Chemistry, Vol. 79, No. 13, 2007, pp. 4900-4907. doi:10.1021/ac070189y
P. Mallikaratchy, Z. Tang, S. Kwame, L. Meng, D. Shangguan and W. Tan, “Aptamer Directly Evolved from Live Cells Recognizes Membrane Bound Immunoglobin Heavy Mu Chain in Burkitt’s Lymphoma Cells,” Molecular & Cellular Proteomics, Vol. 6, No. 12, 2007, pp. 2230-2238. doi:10.1074/mcp.M700026-MCP200
H. Shi, Z. Tang, Y. Kim, H. Nie, Y. F. Huang, X. He, et al., “In Vivo Fluorescence Imaging of Tumors Using Molecular Aptamers Generated by Cell-SELEX,” Chemistry, an Asian Journal, Vol. 5, No. 10, 2010, pp. 2209-2213. doi:10.1002/asia.201000242
P. Gong, B. Shi, M. Zheng, B. Wang, P. Zhang, D. Hu, et al., “PEI Protected Aptamer Molecular Probes for Contrast-Enhanced in Vivo Cancer Imaging,” Biomaterials, Vol. 33, No. 31, 2012, pp. 7810-7817. doi:10.1016/j.biomaterials.2012.07.011
G. Liu, X. Mao, J. A. Phillips, H. Xu, W. Tan and L. Zeng, “Aptamer-Nanoparticle Strip Biosensor for Sensitive Detection of Cancer Cells,” Analytical Chemistry, Vol. 81, No. 24, 2009, pp. 10013-10018. doi:10.1021/ac901889s
D. Shangguan, Y. Li, Z. Tang, Z. C. Cao, H. W. Chen, P. Mallikaratchy, et al., “Aptamers Evolved from Live Cells as Effective Molecular Probes for Cancer Study,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 103. No. 32, 2006, pp. 11838-11843. doi:10.1073/pnas.0602615103
D. Shangguan, Z. Cao, L. Meng, P. Mallikaratchy, K. Sefah, H. Wang, et al., “Cell-Specific Aptamer Probes for Membrane Protein Elucidation in Cancer Cells,” Journal of Proteome Research, Vol. 7, No. 5, 2008, pp. 2133-2139. doi:10.1021/pr700894d
G. Jiang, M. Zhang, B. Yue, M. Yang, C. Carter, S. Z. Al-Quran, et al., “PTK7: A New Biomarker for Immunophenotypic Characterization of Maturing T Cells and T Cell Acute Lymphoblastic Leukemia,” Leukemia Research, Vol. 36, No. 11, 2012, pp. 1347-1353. doi:10.1016/j.leukres.2012.07.004
H. Shi, X. He, K. Wang, X. Wu, X. Ye, Q. Guo, et al., “Activatable Aptamer Probe for Contrast-Enhanced in Vivo Cancer Imaging Based on Cell Membrane Protein-Triggered Conformation Alteration,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 108. No. 10, 2011, pp. 3900-3905. doi:10.1073/pnas.1016197108
Y. Xu, J. A. Phillips, J. Yan, Q. Li, Z. H. Fan and W. Tan, “Aptamer-Based Microfluidic Device for Enrichment, Sorting, and Detection of Multiple Cancer Cells,” Analytical Chemistry, Vol. 81, No. 17, 2009, pp. 7436-7442. doi:10.1021/ac9012072
J. A. Phillips, Y. Xu, Z. Xia, Z. H. Fan and W. Tan, “Enrichment of Cancer Cells Using Aptamers Immobilized on a Microfluidic Channel,” Analytical Chemistry, Vol. 81, No. 3, 2009, pp. 1033-1039. doi:10.1021/ac802092j
J. H. Lee, “Conjugation Approaches for Construction of Aptamer-Modified Nanoparticles for Application in Imaging,” Current Topics in Medicinal Chemistry, Vol. 13, No. 4, 2013, pp. 504-512.
Y. F. Huang, H. T. Chang and W. Tan, “Cancer Cell Targeting Using Multiple Aptamers Conjugated on Nanorods,” Analytical Chemistry, Vol. 80, No. 3, 2008, pp. 567-572. doi:10.1021/ac702322j
E. Ayala, “Hematopoietic Cell Transplantation for B-Cell Lymphoma: An Update,” Cancer Control: Journal of the Moffitt Cancer Center, Vol. 19, No. 3, 2012, pp. 175-186.
S. M. Nimjee, C. P. Rusconi and B. A. Sullenger, “Aptamers: An Emerging Class of Therapeutics,” Annual Review of Medicine, Vol. 56, 2005, pp. 555-583. doi:10.1146/annurev.med.56.062904.144915
D. H. Bunka and P. G. Stockley, “Aptamers Come of Age—At Last,” Nature Reviews Microbiology, Vol. 4, No. 8, 2006, pp. 588-596.
P. J. Bates, D. A. Laber, D. M. Miller, S. D. Thomas and J. O. Trent, “Discovery and Development of the G-Rich Oligonucleotide AS1411 as a Novel Treatment for Cancer,” Experimental and Molecular Pathology, Vol. 86, No. 3, 2009, pp. 151-164. doi:10.1016/j.yexmp.2009.01.004
A. C. Girvan, Y. Teng, L. K. Casson, S. D. Thomas, S. Juliger, M. W. Ball, et al., “AGRO100 Inhibits Activation of Nuclear Factor-kappaB (NF-kappaB) by Forming a Complex with NF-kappaB Essential Modulator (NEMO) and Nucleolin,” Molecular Cancer Therapeutics, Vol. 5, No. 7, 2006, pp. 1790-1799.
S. Gattoni-Celli, C. L. Buckner, J. Lazarchick, R. K. Stuart and D. J. Fernandes, “Overexpression of Nucleolin in Engrafted Acute Myelogenous Leukemia Cells,” American Journal of Hematology, Vol. 84, No. 8, 2009, pp. 535-538. doi:10.1002/ajh.21461
N. Tulchin, M. Chambon, G. Juan, S. Dikman, J. Strauchen, L. Ornstein, et al., “BRCA1 Protein and Nucleolin Colocalize in Breast Carcinoma Tissue and Cancer Cell Lines,” The American Journal of Pathology, Vol. 176, No. 3, 2010, pp. 1203-1214. doi:10.2353/ajpath.2010.081063
L. Peng, J. Liang, H. Wang, X. Song, A. Rashid, H. F. Gomez, et al., “High Levels of Nucleolar Expression of Nucleolin Are Associated with Better Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma,” Clinical Cancer Research, Vol. 16, No. 14, 2010, pp. 3734-3742. doi:10.1158/1078-0432.CCR-09-3411
H. Zhao, Y. Huang, C. Xue, Y. Chen, X. Hou, Y. Guo, et al., “Prognostic Significance of the Combined Score of Endothelial Expression of Nucleolin and CD31 in Surgically Resected Non-Small Cell Lung Cancer,” PloS One, Vol. 8, No. 1, 2013, p. e54674. doi:10.1371/journal.pone.0054674
F. Mongelard and P. Bouvet, “AS-1411, a GuanosineRich Oligonucleotide Aptamer Targeting Nucleolin for the Potential Treatment of Cancer, Including Acute Myeloid Leukemia,” Current Opinion in Molecular Therapeutics, Vol. 12, No. 1, 2010, pp. 107-114.
Y. Shang, S. Kakinuma, M. Nishimura, Y. Kobayashi, K. Nagata and Y. Shimada, “Interleukin-9 Receptor Gene Is Transcriptionally Regulated by Nucleolin in T-Cell Lymphoma Cells,” Molecular Carcinogenesis, Vol. 51, No. 8, 2012, pp. 619-627. doi:10.1002/mc.20834
Y. Otake, S. Soundararajan, T. K. Sengupta, E. A. Kio, J. C. Smith, M. Pineda-Roman, et al., “Overexpression of Nucleolin in Chronic Lymphocytic Leukemia Cells Induces Stabilization of bcl2 mRNA,” Blood, Vol. 109, No. 7, 2007, pp. 3069-3075. doi:10.1182/blood-2006-08-043257
Y. A. Shieh, S. J. Yang, M. F. Wei and M. J. Shieh, “Aptamer-Based Tumor-Targeted Drug Delivery for Photodynamic Therapy,” ACS Nano, Vol. 4, No. 3, 2010, pp. 1433-1442. doi:10.1021/nn901374b
A. Vater and S. Klussmann, “Toward Third-Generation Aptamers: Spiegelmers and Their Therapeutic Prospects,” Current Opinion in Drug Discovery & Development, Vol. 6, No. 2, 2003, pp. 253-261.
D. Eulberg and S. Klussmann, “Spiegelmers: Biostable Aptamers,” Chembiochem: A European Journal of Chemical Biology, Vol. 4, No. 10, 2003, pp. 979-983. doi:10.1002/cbic.200300663
D. G. Duda, S. V. Kozin, N. D. Kirkpatrick, L. Xu, D. Fukumura and R. K. Jain, “CXCL12 (SDF1alpha)CXCR4/CXCR7 Pathway Inhibition: An Emerging Sensitizer for Anticancer Therapies?” Clinical Cancer Research, Vol. 17, No. 8, 2011, pp. 2074-2080. doi:10.1158/1078-0432.CCR-10-2636
M. Borge, P. R. Nannini, P. E. Morande, C. Jancic, A. Bistmans, R. F. Bezares, et al., “CXCL12 Is a Costimulator for CD4+ T Cell Activation and Proliferation in Chronic Lymphocytic Leukemia Patients,” Cancer Immunology, Immunotherapy, Vol. 62, No. 1, 2013, pp. 113-124. doi:10.1007/s00262-012-1320-7
J. R. Adair, P. W. Howard, J. A. Hartley, D. G. Williams and K. A. Chester, “Antibody-Drug Conjugates—A Perfect Synergy,” Expert Opinion on Biological Therapy, Vol. 12, No. 9, 2012, pp. 1191-1206. doi:10.1517/14712598.2012.693473
M. A. Firer and G. Gellerman, “Targeted Drug Delivery for Cancer Therapy: The Other Side of Antibodies,” Journal of Hematology & Oncology, Vol. 5, 2012, pp. 70.
R. Stasi, “Gemtuzumab Ozogamicin: An Anti-CD33 Immunoconjugate for the Treatment of Acute Myeloid Leukaemia,” Expert Opinion on Biological Therapy, Vol. 8, No. 4, 2008, pp. 527-540. doi:10.1517/14712598.8.4.527
B. Pro and G. F. Perini, “Brentuximab Vedotin in Hodgkin’s Lymphoma,” Expert Opinion on Biological Therapy, Vol. 12, No. 10, 2012, pp. 1415-1421. doi:10.1517/14712598.2012.718328
K. Haddley, “Brentuximab Vedotin: Its Role in the Treatment of Anaplastic Large Cell and Hodgkin’s Lymphoma,” Drugs of Today, Vol. 48, No. 4, 2012, pp. 259-270.
M. Furtado and S. Rule, “Emerging Pharmacotherapy for Relapsed or Refractory Hodgkin’s Lymphoma: Focus on Brentuximab Vedotin,” Clinical Medicine Insights Oncology, Vol. 6, 2012, pp. 31-39.
G. P. Canellos, “Brentuximab Vedotin and Panobinostat: New Drugs for Hodgkin’s Lymphoma—Can They Make One of Medical Oncology’s Chemotherapy Success Stories More Successful?” Journal of Clinical Oncology, Vol. 30, No. 18, 2012, pp. 2171-2172. doi:10.1200/JCO.2011.39.6416
A. Younes, A. K. Gopal, S. E. Smith, S. M. Ansell, J. D. Rosenblatt, K. J. Savage, et al., “Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients with Relapsed or Refractory Hodgkin’s Lymphoma,” Journal of Clinical Oncology, Vol. 30, No. 18, 2012, pp. 2183-2189. doi:10.1200/JCO.2011.38.0410
P. F. Bross, J. Beitz, G. Chen, X. H. Chen, E. Duffy, L. Kieffer, et al., “Approval Summary: Gemtuzumab Ozogamicin in Relapsed Acute Myeloid Leukemia,” Clinical Cancer Research, Vol. 7, No. 6, 2001, pp. 1490-1496.
P. Mallikaratchy, Z. Tang and W. Tan, “Cell Specific Aptamer-Photosensitizer Conjugates as a Molecular Tool in Photodynamic Therapy,” ChemMedChem, Vol. 3, No. 3, 2008, pp. 425-428. doi:10.1002/cmdc.200700260
F. Schmitt and L. Juillerat-Jeanneret, “Drug Targeting Strategies for Photodynamic Therapy,” Anti-Cancer Agents in Medicinal Chemistry, Vol. 12, No. 5, 2012, pp. 500-525. doi:10.2174/187152012800617830
Y. Wu, K. Sefah, H. Liu, R. Wang and W. Tan, “DNA Aptamer-Micelle as an Efficient Detection/Delivery Vehicle toward Cancer Cells,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 1, 2010, pp. 5-10. doi:10.1073/pnas.0909611107
M. Barel, K. Meibom and A. Charbit, “Nucleolin, a Shuttle Protein Promoting Infection of Human Monocytes by Francisella Tularensis,” PloS One, Vol. 5, No. 12, 2010, p. e14193. doi:10.1371/journal.pone.0014193
A. Aravind, P. Jeyamohan, R. Nair, S. Veeranarayanan, Y. Nagaoka, Y. Yoshida, et al., “AS1411 Aptamer Tagged PLGA-Lecithin-PEG Nanoparticles for Tumor Cell Targeting and Drug Delivery,” Biotechnology and Bioengineering, Vol. 109, No. 11, 2012, pp. 2920-2931. doi:10.1002/bit.24558
J. W. Kotula, E. D. Pratico, X. Ming, O. Nakagawa, R. L. Juliano and B. A. Sullenger, “Aptamer-Mediated Delivery of Splice-Switching Oligonucleotides to the Nuclei of Cancer Cells,” Nucleic Acid Therapeutics, Vol. 22, No. 3, 2012, pp. 187-195.
J. K. Kim, K. J. Choi, M. Lee, M. H. Jo and S. Kim, “Molecular Imaging of a Cancer-Targeting Theragnostics Probe Using a Nucleolin Aptamerand microRNA-221 Molecular Beacon-Conjugated Nanoparticle,” Biomaterials, Vol. 33, No. 1, 2012, pp. 207-217. doi:10.1016/j.bioma terials.2011.09.023
Y. F. Huang, D. Shangguan, H. Liu, J. A. Phillips, X. Zhang, Y. Chen, et al., “Molecular Assembly of an Aptamer-Drug Conjugate for Targeted Drug Delivery to Tumor Cells,” Chembiochem, Vol. 10, No. 5, 2009, pp. 862-868. doi:10.1002/cbic.200800805
S. M. Taghdisi, K. Abnous, F. Mosaffa and J. Behravan, “Targeted Delivery of Daunorubicin to T-Cell Acute Lymphoblastic Leukemia by Aptamer,” Journal of Drug Targeting, Vol. 18, No. 4, 2010, pp. 277-281. doi:10.3109/10611860903434050
H. Kang, M. B. O’Donoghue, H. Liu and W. Tan, “A liposome-Based Nanostructure for Aptamer Directed Delivery,” Chemical Communications, Vol. 46, No. 2, 2010, pp. 249-251. doi:10.1039/b916911c
C. H. Wang, S. T. Kang, Y. H. Lee, Y. L. Luo, Y. F. Huang and C. K. Yeh, “Aptamer-Conjugated and DrugLoaded Acoustic Droplets for Ultrasound Theranosis,” Biomaterials, Vol. 33, No. 6, 2012, pp. 1939-1947. doi:10.1016/j.biomaterials.2011.11.036
J. Liu, H. Liu, H. Kang, M. Donovan, Z. Zhu and W. Tan, “Aptamer-Incorporated Hydrogels for Visual Detection, Controlled Drug Release, and Targeted Cancer Therapy,” Analytical and Bioanalytical Chemistry, Vol. 402, No. 1, 2012, pp. 187-194. doi:10.1007/s00216-011-5414-4
H. Kang, H. Liu, X. Zhang, J. Yan, Z. Zhu, L. Peng, et al., “Photoresponsive DNA-Cross-Linked Hydrogels for Controllable Release and Cancer Therapy,” Langmuir, Vol. 27, No. 1, 2011, pp. 399-408. doi:10.1021/la1037553
G. J. Tong, S. C. Hsiao, Z. M. Carrico and M. B. Francis, “Viral Capsid DNA Aptamer Conjugates as Multivalent Cell-Targeting Vehicles,” Journal of the American Chemical Society, Vol. 131, No. 31, 2009, pp. 11174-11178. doi:10.1021/ja903857f
N. Stephanopoulos, G. J. Tong, S. C. Hsiao and M. B. Francis, “Dual-Surface Modified Virus Capsids for Targeted Delivery of Photodynamic Agents to Cancer Cells,” ACS Nano, Vol. 4, No. 10, 2010, pp. 6014-6020. doi:10.1021/nn1014769
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, 2011, p. 2.
A. D. Keefe, S. Pai and A. Ellington, “Aptamers as Therapeutics,” Nature Reviews, Vol. 9, No. 7, 2010, pp. 537-550.
P. S. Pendergrast, H. N. Marsh, D. Grate, J. M. Healy and M. Stanton, “Nucleic Acid Aptamers for Target Validation and Therapeutic Applications,” Journal of Biomolecular Techniques, Vol. 16, No. 3, 2005, pp. 224-234.
A. D. Keefe and R. G. Schaub, “Aptamers as Candidate Therapeutics for Cardiovascular Indications,” Current Opinion in Pharmacology, Vol. 8, No. 2, 2008, pp. 147-152.
J. Haasnoot and B. Berkhout, “Nucleic Acids-Based Therapeutics in the Battle against Pathogenic Viruses,” Handbook of Experimental Pharmacology, Vol. 189, 2009, pp. 243-263. doi:10.1007/978-3-540-79086-0_9
J. C. Burnett and J. J. Rossi, “RNA-Based Therapeutics: Current Progress and Future Prospects,” Chemistry & Biology, Vol. 19, No. 1, 2012, pp. 60-71.
M. H. Caruthers, “The Chemical Synthesis of DNA/RNA: Our Gift to Science,” The Journal of Biological Chemistry, Vol. 288, 2012, pp. 1420-1427. doi:10.1074/jbc.X112.442855
J. Zhou, P. Swiderski, H. Li, J. Zhang, C. P. Neff, R. Akkina, et al., “Selection, Characterization and Application of New RNA HIV GP 120 Aptamers for Facile Delivery of Dicer Substrate siRNAs into HIV Infected Cells,” Nucleic Acids Research, Vol. 37, No. 9, 2009, pp. 3094-3109. doi:10.1093/nar/gkp185
A. Schroeder, C. G. Levins, C. Cortez, R. Langer and D. G. Anderson, “Lipid-Based Nanotherapeutics for siRNA Delivery,” Journal of Internal Medicine, Vol. 267. No. 1, 2010, pp. 9-21.
J. Nguyen and F. C. Szoka, “Nucleic acid Delivery: The Missing Pieces of the Puzzle?” Accounts of Chemical Research, Vol. 45, No. 7, 2012, pp. 1153-1162. doi:10.1021/ar3000162
S. Mukherjee, R. N. Ghosh and F. R. Maxfield, “Endocytosis,” Physiological Reviews, Vol. 77, No. 3, 1997, pp. 759-803.
S. Kumari, S. Mg and S. Mayor, “Endocytosis Unplugged: Multiple Ways to Enter the Cell,” Cell Research, Vol. 20, No. 3, 2010, pp. 256-275.
J. Schafer, S. Hobel, U. Bakowsky and A. Aigner, “Liposome-Polyethylenimine Complexes for Enhanced DNA and siRNA Delivery,” Biomaterials, Vol. 31, No. 26, 2010, pp. 6892-6900.
M. Gunther, J. Lipka, A. Malek, D. Gutsch, W. Kreyling and A. Aigner, “Polyethylenimines for RNAi-Mediated Gene Targeting in Vivo and siRNA Delivery to the Lung,” European Journal of Pharmaceutics and Biopharmaceutics, Vol. 77, No. 3, 2011, pp. 438-449.
S. Y. Wu and N. A. McMillan, “Lipidic Systems for in Vivo siRNA Delivery,” AAPS Journal, Vol. 11, No. 4, 2009, pp. 639-652. doi:10.1208/s12248-009-9140-1
Y. Sakurai, H. Hatakeyama, Y. Sato, H. Akita, K. Takayama, S. Kobayashi, et al., “Endosomal Escape and the Knockdown Efficiency of Liposomal-siRNA by the Fusogenic Peptide shGALA,” Biomaterials, Vol. 32, No. 24, 2011, pp. 5733-5742.
K. W. Thiel, L. I. Hernandez, J. P. Dassie, W. H. Thiel, X. Liu, K. R. Stockdale, et al., “Delivery of Chemo-Sensitizing siRNAs to HER2+-Breast Cancer Cells Using RNA Aptamers,” Nucleic Acids Research, Vol. 40, No. 13, 2012, pp. 6319-6337
P. Guo, “The Emerging Field of RNA Nanotechnology,” Nature Nanotechnology, Vol. 5, No. 12, 2010, pp. 833-842.
G. C. Shukla, F. Haque, Y. Tor, L. M. Wilhelmsson, J. J. Toulme, H. Isambert, et al., “A Boost for the Emerging Field of RNA Nanotechnology,” ACS Nano, Vol. 5, No. 5, 2011, pp. 3405-3418. doi:10.1021/nn200989r
J. J. Rossi, “RNA Nanoparticles Come of Age,” Acta Biochimica et Biophysica Sinica, Vol. 43, No. 4, 2011, pp. 245-247. doi:10.1093/abbs/gmr018