Display options
Cite
Cheetham AG, Zhang P, Lin YA, et al. Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin. J Mater Chem B. 2014;2(42):7316-7326doi: 10.1039/C4TB01084A.
Cheetham, A. G., Zhang, P., Lin, Y. A., Lin, R., & Cui, H. (2014). Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin. Journal of materials chemistry. B, 2(42), 7316-7326. https://doi.org/10.1039/C4TB01084A
Cheetham, A G, et al. "Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin." Journal of materials chemistry. B vol. 2,42 (2014): 7316-7326. doi: https://doi.org/10.1039/C4TB01084A
Cheetham AG, Zhang P, Lin YA, Lin R, Cui H. Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin. J Mater Chem B. 2014 Nov 14;2(42):7316-7326. doi: 10.1039/C4TB01084A. PMID: 25667746; PMCID: PMC4319564.
Copy Download .nbib Format: NLM
Share it on

J Mater Chem B. 2014 Nov 14;2(42):7316-7326. doi: 10.1039/C4TB01084A.

Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin.

Journal of materials chemistry. B

A G Cheetham, P Zhang, Y-A Lin, R Lin, H Cui

Affiliations

  1. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA ; Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
  2. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.

PMID: 25667746 PMCID: PMC4319564 DOI: 10.1039/C4TB01084A

Abstract

Self-assembly of anticancer therapeutics into discrete nanostructures provides an innovative way to develop a self-delivering nanomedicine with a high, quantitative drug loading. We report here the synthesis and assembly of a mikto-arm star dual drug amphiphile (DA) containing both a bulky paclitaxel (PTX) and a planar camptothecin (CPT). The two anti-cancer drugs of interest were stochastically conjugated to a β-sheet forming peptide (Sup35) and under physiologically-relevant conditions the dual DA could spontaneously associate into supramolecular filaments with a fixed 41% total drug loading (29% PTX and 12% CPT). Transmission electron microscopy imaging and circular dichroism spectroscopy studies reveal that the bulkiness of the PTX, as well as the π-π interaction preference between the CPT units, has a significant impact on the assembly kinetics, molecular level packing, and nanostructure morphology and stability. We found that the DA containing two PTX units assembled into non-filamentous micelle-like structures, in contrast to the filamentous structures formed by the hetero dual DA and the DA containing two CPTs. The hetero dual DA was found to effectively release the two anticancer agents, exhibiting superior cytotoxicity against PTX-resistant cervical cancer cells. The presented work offers a potential method to generate well-defined entwined filamentous nanostructures and provides the basis for a future combination therapy platform.

References

  1. Nat Nanotechnol. 2007 Apr;2(4):249-55 - PubMed
  2. J Am Chem Soc. 2010 May 5;132(17):6041-6 - PubMed
  3. J Am Chem Soc. 2009 Sep 30;131(38):13576-7 - PubMed
  4. Science. 2012 Feb 17;335(6070):813-7 - PubMed
  5. Chem Soc Rev. 2008 Apr;37(4):664-75 - PubMed
  6. Nat Rev Drug Discov. 2008 Sep;7(9):771-82 - PubMed
  7. Chem Commun (Camb). 2014 Jun 7;50(45):6039-42 - PubMed
  8. Chem Commun (Camb). 2011 Aug 14;47(30):8647-9 - PubMed
  9. Biomacromolecules. 2011 Jul 11;12(7):2735-45 - PubMed
  10. Biopolymers. 2010;94(1):1-18 - PubMed
  11. Science. 1991 Nov 29;254(5036):1312-9 - PubMed
  12. J Control Release. 2007 Dec 4;124(1-2):20-7 - PubMed
  13. Nat Rev Cancer. 2006 Oct;6(10):789-802 - PubMed
  14. Bioconjug Chem. 2004 Nov-Dec;15(6):1314-21 - PubMed
  15. Chem Asian J. 2014 Jun;9(6):1446-72 - PubMed
  16. J Struct Biol. 1995 Jul-Aug;115(1):1-15 - PubMed
  17. J Am Chem Soc. 2006 Jun 7;128(22):7390-8 - PubMed
  18. Chem Commun (Camb). 2013 May 28;49(43):4968-70 - PubMed
  19. Angew Chem Int Ed Engl. 2013 Jul 1;52(27):6944-8 - PubMed
  20. Org Biomol Chem. 2013 Jan 14;11(2):219-32 - PubMed
  21. Nat Mater. 2009 Jul;8(7):596-600 - PubMed
  22. Chem Soc Rev. 2010 Aug;39(8):2817-26 - PubMed
  23. J Am Chem Soc. 2000 Jun 7;122(22):5262-77 - PubMed
  24. J Phys Chem B. 2006 May 11;110(18):9027-33 - PubMed
  25. Adv Drug Deliv Rev. 2004 Sep 22;56(11):1537-63 - PubMed
  26. J Colloid Interface Sci. 2005 Apr 1;284(1):282-8 - PubMed
  27. Biochemistry. 2009 Apr 21;48(15):3304-14 - PubMed
  28. Acc Chem Res. 2013 Jul 16;46(7):1527-37 - PubMed
  29. Chem Commun (Camb). 2014 Mar 14;50(21):2772-4 - PubMed
  30. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12128-33 - PubMed
  31. N Engl J Med. 1995 Apr 13;332(15):1004-14 - PubMed
  32. Adv Drug Deliv Rev. 2009 Nov 12;61(13):1203-13 - PubMed
  33. Mol Pharm. 2013 Mar 4;10 (3):867-74 - PubMed
  34. J Am Chem Soc. 2006 May 3;128(17):5923-9 - PubMed
  35. ACS Nano. 2011 Nov 22;5(11):9113-21 - PubMed
  36. Biomaterials. 2008 Dec;29(34):4501-9 - PubMed
  37. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1744-9 - PubMed
  38. Nature. 2005 Jun 9;435(7043):773-8 - PubMed
  39. ACS Macro Lett. 2013 Dec 17;2(12):1088-1094 - PubMed
  40. Angew Chem Int Ed Engl. 2013 Feb 4;52(6):1683-7 - PubMed
  41. J Am Chem Soc. 2006 Jun 7;128(22):7291-8 - PubMed
  42. Mol Membr Biol. 2011 Jan;28(1):42-53 - PubMed
  43. J Am Chem Soc. 2010 Mar 31;132(12):4259-65 - PubMed
  44. Prion. 2009 Apr-Jun;3(2):89-93 - PubMed
  45. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9196-201 - PubMed
  46. Curr Oncol. 2007 Oct;14(5):189-94 - PubMed
  47. Chem Commun (Camb). 2012 Jan 11;48(3):395-7 - PubMed
  48. ACS Nano. 2013 Oct 22;7(10):9055-63 - PubMed
  49. J Am Chem Soc. 2013 Feb 27;135(8):2907-10 - PubMed
  50. J Am Chem Soc. 2013 Nov 13;135(45):16789-92 - PubMed
  51. EMBO J. 1999 Feb 15;18(4):815-21 - PubMed
  52. Angew Chem Int Ed Engl. 2013 Sep 27;52(40):10537-40 - PubMed
  53. Biomacromolecules. 2014 Apr 14;15(4):1171-84 - PubMed
  54. J Am Chem Soc. 2006 Oct 11;128(40):13298-304 - PubMed
  55. Int J Pharm. 2006 Feb 17;309(1-2):199-207 - PubMed
  56. Angew Chem Int Ed Engl. 2012 Jul 2;51(27):6572-81 - PubMed
  57. J Pharm Sci. 1994 Oct;83(10 ):1470-6 - PubMed
  58. Chemistry. 2010 Aug 16;16(31):9544-54 - PubMed
  59. Faraday Discuss. 2013;166:285-301 - PubMed
  60. J Am Chem Soc. 2002 Feb 20;124(7):1269-75 - PubMed
  61. Nat Rev Cancer. 2006 Sep;6(9):688-701 - PubMed
  62. Biomacromolecules. 2013 May 13;14(5):1370-8 - PubMed
  63. Nat Mater. 2009 Dec;8(12):993-9 - PubMed
  64. Science. 1995 Mar 17;267(5204):1635-8 - PubMed
  65. Oncol Rep. 2011 May;25(5):1473-80 - PubMed
  66. Biochem Pharmacol. 1998 Apr 15;55(8):1163-74 - PubMed
  67. Biomacromolecules. 2014 May 12;15(5):1543-59 - PubMed

Publication Types

Grant support