Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
Cancer chemotherapy has been limited by its side effects and multidrug resistance (MDR), the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers (NFs) for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin (Dox)-binding DNA for drug delivery. NF sizes are tunable (down to ~200 nm in diameter), and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity (71.4%, wt/wt). Although the Doxloaded NFs (NF-Dox) are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.
Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004, 56, 185-229.
Holohan, C.; Van Schaeybroeck, S.; Longley, D. B.; Johnston, P. G. Cancer drug resistance: An evolving paradigm. Nat. Rev. Cancer 2013, 13, 714-726.
Wiernik, P. H. Anthracyclines: Current status and new development. Academic Press, NY 1980.
Chatterjee, K.; Zhang, J. Q.; Honbo, N.; Karliner, J. S. Doxorubicin cardiomyopathy. Cardiol. 2010, 115, 155-162.
Szakacs, G.; Paterson, J. K.; Ludwig, J. A.; Booth-Genthe, C.; Gottesman, M. M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 2006, 5, 219-234.
Gottesman, M. M.; Fojo, T.; Bates, S. E. Multidrug resistance in cancer: Role of atp-dependent transporters. Nat. Rev. Cancer 2002, 2, 48-58.
Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q.; Urbatsch, I. L. et al. Structure of p-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 2009, 323, 1718-1722.
Burns, J. S.; Abdallah, B. M.; Guldberg, P.; Rygaard, J.; Schroder, H. D.; Kassem, M. Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells. Cancer Res. 2005, 65, 3126-3135.
Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2, 751-760.
Hughes, B. Antibody-drug conjugates for cancer: Poised to deliver? Nat. Rev. Drug Discov. 2010, 9, 665-667.
Zhu, G.; Ye, M.; Donovan, M. J.; Song, E.; Zhao, Z.; Tan, W. Nucleic acid aptamers: An emerging frontier in cancer therapy. Chem. Comm. 2012, 10472-10480.
Santra, S.; Kaittanis, C.; Santiesteban, O. J.; Perez, J. M. Cell- specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. J. Am. Chem. Soc. 2011, 133, 16680-16688.
Ellington, A. D.; Szostak, J. W. In vitro selection of rna molecules that bind specific ligands. Nature 1990, 346, 818-822.
Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: Rna ligands to bacteriophage t4 DNA polymerase. Science 1990, 249, 505-510.
Shangguan, D. H.; Li, Y.; Tang, Z. W.; Cao, Z.; Chen, H. W.; Mallikaratchy, P.; Sefah, K.; Yang, C. J.; Tan, W. Aptamers evolved from live cells as effective molecular probes for cancer study. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 11838-11843.
Sefah, K.; Tang, Z.; Shangguan, D.; Chen, H.; Lopez-Colon, D.; Li, Y.; Parekh, P.; Martin, J.; Meng, L.; Phillips, J. A. et al. Molecular recognition of acute myeloid leukemia using aptamers. Leukemia 2009, 23, 235-244.
Tang, Z.; Shangguan, D. H.; Wang, K.; Shi, H.; Sefah, K.; Mallikaratchy, P.; Chen, H. W.; Li, Y.; Tan, W. Selection of aptamers for molecular recognition and characterization of cancer cells. Anal. Chem. 2007, 79, 4900-4907.
Group, T. E. S. Preclinical and phase 1a clinical evaluation of an anti-vegf pegylated aptamer (eye001) for the treatment of exudative age-related macular degeneration. Retina 2002, 2, 143-152.
Keefe, A. D.; Pai, S.; Ellington, A. Aptamers as therapeutics. Nat. Rev. Drug Discov. 2010, 9, 537-550.
Petros, R. A.; DeSimone, J. M. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 2010, 9, 615-627.
MacDiarmid, J. A.; Amaro-Mugridge, N. B.; Madrid-Weiss, J.; Sedliarou, I.; Wetzel, S.; Kochar, K.; Brahmbhatt, V. N.; Phillips, L.; Pattison, S. T.; Petti, C. et al. Sequential treatment of drug-resistant tumors with targeted minicells containing sirna or a cytotoxic drug. Nat. Biotechnol. 2009, 27, 643-651.
Jiang, Q.; Song, C.; Nangreave, J.; Liu, X. W.; Lin, L.; Qiu, D. L.; Wang, Z. G.; Zou, G. Z.; Liang, X. J.; Yan, H. et al. DNA origami as a carrier for circumvention of drug resistance. J. Am. Chem. Soc. 2012, 134, 13396-13403.
Wang, F.; Wang, Y. C.; Dou, S.; Xiong, M. H.; Sun, T. M.; Wang, J. Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. ACS Nano 2011, 5, 3679-3692.
Li, R.; Wu, R.; Zhao, L.; Wu, M.; Yang, L.; Zou, H. P-glycoprotein antibody functionalized carbon nanotube overcomes the multidrug resistance of human leukemia cells. ACS Nano 2010, 4, 1399-1408.
Chow, E. K.; Zhang, X. Q.; Chen, M.; Lam, R.; Robinson, E.; Huang, H.; Schaffer, D.; Osawa, E.; Goga, A.; Ho, D. Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci. Transl. Med. 2011, 3, 73ra21.
Meng, H.; Mai, W. X.; Zhang, H.; Xue, M.; Xia, T.; Lin, S.; Wang, X.; Zhao, Y.; Ji, Z.; Zink, J. I. et al. Codelivery of an optimal drug/sirna combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano 2013, 7, 994-1005.
Xue, X.; Hall, M. D.; Zhang, Q.; Wang, P. C.; Gottesman, M. M.; Liang, X. J. Nanoscale drug delivery platforms overcome platinum-based resistance in cancer cells due to abnormal membrane protein trafficking. ACS Nano 2013, 7, 10452-10464.
Yang, L.; Meng, L.; Zhang, X. B.; Chen, Y.; Zhu, G. Z.; Liu, H. P.; Xiong, X. L.; Sefah, K.; Tan, W. H. Engineering polymeric aptamers for selective cytotoxicity. J. Am. Chem. Soc. 2011, 133, 13380-13386.
Wu, C. C.; Han, D.; Chen, T.; Peng, L.; Zhu, G. Z.; You, M. X.; Qiu, L. P.; Sefah, K.; Zhang, X. B.; Tan, W. H. Building a multifunctional aptamer-based DNA nanoassembly for targeted cancer therapy. J. Am. Chem. Soc. 2013, 135, 18644-18650.
Kang, H.; Trondoli, A. C.; Zhu, G.; Chen, Y.; Chang, Y. J.; Liu, H.; Huang, Y. F.; Zhang, X.; Tan, W. Near-infrared light-responsive core-shell nanogels for targeted drug delivery. ACS Nano 2011, 5, 5094-5099.
Bhirde, A. A.; Chikkaveeraiah, B. V.; Srivatsan, A.; Niu, G.; Jin, A. J.; Kapoor, A.; Wang, Z.; Patel, S.; Patel, V.; Gorbach, A. M. et al. Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance. ACS Nano 2014, 8, 4177-4189.
Seeman, N. C. Nanomaterials based on DNA. Annu. Rev. Biochem. 2010, 79, 65-87.
Li, J.; Pei, H.; Zhu, B.; Liang, L.; Wei, M.; He, Y.; Chen, N.; Li, D.; Huang, Q.; Fan, C. H. Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory cpg oligonucleotides. ACS nano 2011, 5, 8783-8789.
Zhu, G. Z.; Zheng, J.; Song, E.; Donovan, M.; Zhang, K. J.; Liu, C.; Tan, W. H. Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 7998-8003.
Zhu, G.; Meng, L.; Ye, M.; Yang, L.; Sefah, K.; O'Donoghue, M. B.; Chen, Y.; Xiong, X.; Huang, J.; Song, E. et al. Self-assembled aptamer-based drug carriers for bispecific cytotoxicity to cancer cells. Chem. Asian J. 2012, 7, 1630-1636.
Lee, H.; Lytton-Jean, A. K. R.; Chen, Y.; Love, K. T.; Park, A. I.; Karagiannis, E. D.; Sehgal, A.; Querbes, W.; Zurenko, C. S.; Jayaraman, M. et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 2012, 7, 389-393.
Zhu, G. Z.; Hu, R.; Zhao, Z. L.; Chen, Z.; Zhang, X. B.; Tan, W. H. Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications. J. Am. Chem. Soc. 2013, 135, 16438-16445.
Shopsowitz K.; Roh Y.; Deng Z.; Morton S.; Hammond P. RNAi-microsponges form through self-assembly of the organic and inorganic products of transcription. Small 2014, 10, 1623-1633.
Bagalkot, V.; Farokhzad, O. C.; Langer, R.; Jon, S. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew. Chem. Int. Ed. 2006, 45, 8149-8152.
Tamkovich, S. N.; Cherepanova, A. V.; Kolesnikova, E. V.; Rykova, E. Y.; Pyshnyi, D. V.; Vlassov, V. V.; Laktionov, P. P. Circulating DNA and dnase activity in human blood. Ann. N Y Acad. Sci. 2006, 1075, 191-196.
Clarke, R.; Currier, S.; Kaplan, O.; Lovelace, E.; Boulay, V.; Gottesman, M. M.; Dickson, R. B. Effect of p-glycoprotein expression on sensitivity to hormones in mcf-7 human breast cancer cells. J. Natl. Cancer Inst. 1992, 84, 1506-1512.
Langer, R.; Folkman, J. Polymers for the sustained release of proteins and other macromolecules. Nature 1976, 263, 797-800.
Alama, A.; Barbieri, F.; Cagnoli, M.; Schettini, G. Antisense oligonucleotides as therapeutic agents. Pharmacol. Res. 1997, 36, 171-178.
Liu, H.; Moynihan, K. D.; Zheng, Y.; Szeto, G. L.; Li, A. V.; Huang, B.; Van Egeren, D. S.; Park, C.; Irvine, D. J. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 2014, 507, 519-522.